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Intravital Optical Imaging to Monitor Anti-Tumor Immunological Response in Preclinical Models

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Nanoparticle-Mediated Immunotherapy

Part of the book series: Bioanalysis ((BIOANALYSIS,volume 12))

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Abstract

Intravital microscopy is a powerful technique that is uniquely suitable for gaining insight into complex and dynamic interactions between tumor cells, the tumor microenvironment, immune system, other stromal cells, and therapy. There has recently been an expanding interest in understanding these key interactions as they relate to novel and successful immune and targeted therapies for treating cancer. In particular, how these can aid in our understanding of how these complex systems interact and how to understand the determinants of treatment response.

The goal of this chapter is to provide an overview of the technical and biological considerations in carrying out intravital microscopy studies in preclinical models related to imaging immune responses to cancer, with a particular emphasis on nanotechnology mediated therapy and imaging studies.

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References

  1. Secklehner, J., Lo Celso, C., Carlin, L.M.: Intravital microscopy in historic and contemporary immunology. Immunol. Cell Biol. 95, 506–513 (2017). https://doi.org/10.1038/icb.2017.25

    Article  Google Scholar 

  2. Sandison, J.C.: The transparent chamber of the rabbit’s ear, giving a complete description of improved technic of construction and introduction, and general account of growth and behavior of living cells and tissues as seen with the microscope. Am. J. Anat. 41, 447–473 (1928). https://doi.org/10.1002/aja.1000410303

    Article  Google Scholar 

  3. Ide, A., Baker, N., Warren, S.: Vascularization of the Brown Pearce rabbit epithelioma transplant as seen in the transparent ear chamber. Am. J. Roentgenol. 42, 891–899 (1939)

    Google Scholar 

  4. Algire, G.H.: An adaptation of the transparent-chamber technique to the mouse. J. Natl. Cancer Inst. 4, 1–11 (1943). https://doi.org/10.1093/jnci/4.1.1

    Article  Google Scholar 

  5. Gabriel, E.M., Fisher, D.T., Evans, S., Takabe, K., Skitzki, J.J.: Intravital microscopy in the study of the tumor microenvironment: from bench to human application. Oncotarget. 9, 20165–20178 (2018). https://doi.org/10.18632/oncotarget.24957

    Article  Google Scholar 

  6. Ehrlich, P.: Üeber den jetzigen stand der Karzinomforschung. Ned. Tijdschr. Geneeskd. 5, 273–290 (1908)

    Google Scholar 

  7. Mittal, D., Gubin, M.M., Schreiber, R.D., Smyth, M.J.: New insights into cancer immunoediting and its three component phases—elimination, equilibrium and escape. Curr. Opin. Immunol. 27, 16–25 (2014). https://doi.org/10.1016/j.coi.2014.01.004

    Article  Google Scholar 

  8. Shankaran, V., Ikeda, H., Bruce, A.T., White, J.M., Swanson, P.E., Old, L.J., Schreiber, R.D.: IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature. 410, 1107–1111 (2001). https://doi.org/10.1038/35074122

    Article  ADS  Google Scholar 

  9. Alexander, S., Weigelin, B., Winkler, F., Friedl, P.: Preclinical intravital microscopy of the tumour-stroma interface: invasion, metastasis, and therapy response. Curr. Opin. Cell Biol. 25, 659–671 (2013). https://doi.org/10.1016/j.ceb.2013.07.001

    Article  Google Scholar 

  10. Headley, M.B., Bins, A., Nip, A., Roberts, E.W., Looney, M.R., Gerard, A., Krummel, M.F.: Visualization of immediate immune responses to pioneer metastatic cells in the lung. Nature. 531, 513–517 (2016). https://doi.org/10.1038/nature16985

    Article  ADS  Google Scholar 

  11. Hu, F., Martin, H., Martinez, A., Everitt, J., Erkanli, A., Lee, W.T., Dewhirst, M., Ramanujam, N.: Distinct angiogenic changes during carcinogenesis defined by novel label-free dark-field imaging in a hamster cheek pouch model. Cancer Res. 77, 7109–7119 (2017). https://doi.org/10.1158/0008-5472.CAN-17-1058

    Article  Google Scholar 

  12. Schreiber, R.D., Old, L.J., Smyth, M.J.: Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science. 331, 1565–1570 (2011). https://doi.org/10.1126/science.1203486

    Article  ADS  Google Scholar 

  13. Koebel, C.M., Vermi, W., Swann, J.B., Zerafa, N., Rodig, S.J., Old, L.J., Smyth, M.J., Schreiber, R.D.: Adaptive immunity maintains occult cancer in an equilibrium state. Nature. 450, 903–907 (2007). https://doi.org/10.1038/nature06309

    Article  ADS  Google Scholar 

  14. Torcellan, T., Stolp, J., Chtanova, T.: In vivo imaging sheds light on immune cell migration and function in cancer. Front. Immunol. 8, 309 (2017). https://doi.org/10.3389/fimmu.2017.00309

    Article  Google Scholar 

  15. Nakasone, E.S., Askautrud, H.A., Kees, T., Park, J.-H., Plaks, V., Ewald, A.J., Fein, M., Rasch, M.G., Tan, Y.-X., Qiu, J., Park, J., Sinha, P., Bissell, M.J., Frengen, E., Werb, Z., Egeblad, M.: Imaging tumor-stroma interactions during chemotherapy reveals contributions of the microenvironment to resistance. Cancer Cell. 21, 488–503 (2012). https://doi.org/10.1016/j.ccr.2012.02.017

    Article  Google Scholar 

  16. Zal, T., Chodaczek, G.: Intravital imaging of anti-tumor immune response and the tumor microenvironment. Semin. Immunopathol. 32, 305–317 (2010). https://doi.org/10.1007/s00281-010-0217-9

    Article  Google Scholar 

  17. Rosenberg, S.A.: Decade in review—cancer immunotherapy. Nat. Rev. Clin. Oncol. 11, 630–632 (2014). https://doi.org/10.1038/nrclinonc.2014.174

    Article  Google Scholar 

  18. Sharma, P., Wagner, K., Wolchok, J.D., Allison, J.P.: Novel cancer immunotherapy agents with survival benefit: recent successes and next steps. Nat. Rev. Cancer. 11, 805–812 (2011). https://doi.org/10.1038/nrc3153

    Article  Google Scholar 

  19. Blanco, E., Shen, H., Ferrari, M.: Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nat. Biotechnol. 33, 941–951 (2015). https://doi.org/10.1038/nbt.3330

    Article  Google Scholar 

  20. Mitchell, M.J., Jain, R.K., Langer, R.: Engineering and physical sciences in oncology: challenges and opportunities. Nat. Rev. Cancer. 17, 659–675 (2017). https://doi.org/10.1038/nrc.2017.83

    Article  Google Scholar 

  21. Shen, H., Sun, T., Hoang, H.H., Burchfield, J.S., Hamilton, G.F., Mittendorf, E.A., Ferrari, M.: Enhancing cancer immunotherapy through nanotechnology-mediated tumor infiltration and activation of immune cells. Semin. Immunol. 34, 114–122 (2017). https://doi.org/10.1016/j.smim.2017.09.002

    Article  Google Scholar 

  22. Bar-Zeev, M., Livney, Y.D., Assaraf, Y.G.: Targeted nanomedicine for cancer therapeutics: towards precision medicine overcoming drug resistance. Drug Resist. Updat. 31, 15–30 (2017). https://doi.org/10.1016/j.drup.2017.05.002

    Article  Google Scholar 

  23. Dewhirst, M.W., Secomb, T.W.: Transport of drugs from blood vessels to tumour tissue. Nat. Rev. Cancer. 17, 738–750 (2017). https://doi.org/10.1038/nrc.2017.93

    Article  Google Scholar 

  24. Evans, M.K., Brown, M.C., Geradts, J., Bao, X., Robinson, T.J., Jolly, M.K., Vermeulen, P.B., Palmer, G.M., Gromeier, M., Levine, H., Morse, M.A., Van Laere, S.J., Devi, G.R.: XIAP regulation by MNK links MAPK and NFκB signaling to determine an aggressive breast cancer phenotype. Cancer Res. 78, 1726–1738 (2018). https://doi.org/10.1158/0008-5472.CAN-17-1667

    Article  Google Scholar 

  25. Jeanbart, L., Ballester, M., de Titta, A., Corthésy, P., Romero, P., Hubbell, J.A., Swartz, M.A.: Enhancing efficacy of anticancer vaccines by targeted delivery to tumor-draining lymph nodes. Cancer Immunol. Res. 2, 436–447 (2014). https://doi.org/10.1158/2326-6066.CIR-14-0019-T

    Article  Google Scholar 

  26. Liu, H., Moynihan, K.D., Zheng, Y., Szeto, G.L., Li, A.V., Huang, B., Van Egeren, D.S., Park, C., Irvine, D.J.: Structure-based programming of lymph-node targeting in molecular vaccines. Nature. 507, 519–522 (2014). https://doi.org/10.1038/nature12978

    Article  ADS  Google Scholar 

  27. Thomas, S.N., Vokali, E., Lund, A.W., Hubbell, J.A., Swartz, M.A.: Targeting the tumor-draining lymph node with adjuvanted nanoparticles reshapes the anti-tumor immune response. Biomaterials. 35, 814–824 (2014). https://doi.org/10.1016/j.biomaterials.2013.10.003

    Article  Google Scholar 

  28. Andón, F.T., Digifico, E., Maeda, A., Erreni, M., Mantovani, A., Alonso, M.J., Allavena, P.: Targeting tumor associated macrophages: the new challenge for nanomedicine. Semin. Immunol. 34, 103–113 (2017). https://doi.org/10.1016/j.smim.2017.09.004

    Article  Google Scholar 

  29. Batrakova, E.V., Kabanov, A.V.: Pluronic block copolymers. J. Control. Release. 130, 98–106 (2008). https://doi.org/10.1016/j.jconrel.2008.04.013

    Article  Google Scholar 

  30. Fukumura, D., Duda, D.G., Munn, L.L., Jain, R.K.: Tumor microvasculature and microenvironment: novel insights through Intravital imaging in pre-clinical models. Microcirculation. 17, 206–225 (2010). https://doi.org/10.1111/j.1549-8719.2010.00029.x

    Article  Google Scholar 

  31. Nobis, M., Warren, S.C., Lucas, M.C., Murphy, K.J., Herrmann, D., Timpson, P.: Molecular mobility and activity in an intravital imaging setting - implications for cancer progression and targeting. J. Cell Sci. 131 (2018). https://doi.org/10.1242/jcs.206995

  32. Palmer, G.M., Fontanella, A.N., Shan, S., Hanna, G., Zhang, G., Fraser, C.L., Dewhirst, M.W.: In vivo optical molecular imaging and analysis in mice using dorsal window chamber models applied to hypoxia, vasculature and fluorescent reporters. Nat. Protoc. 6, 1355–1366 (2011). https://doi.org/10.1038/nprot.2011.349

    Article  Google Scholar 

  33. Minsky, M.: Memoir on inventing the confocal scanning microscope. Scanning. 10, 128–138 (1988). https://doi.org/10.1002/sca.4950100403

    Article  Google Scholar 

  34. Andresen, V., Pollok, K., Rinnenthal, J.-L., Oehme, L., Günther, R., Spiecker, H., Radbruch, H., Gerhard, J., Sporbert, A., Cseresnyes, Z., Hauser, A.E., Niesner, R.: High-resolution intravital microscopy. PLoS One. 7, e50915 (2012). https://doi.org/10.1371/journal.pone.0050915

    Article  ADS  Google Scholar 

  35. Leong, H.S., Steinmetz, N.F., Ablack, A., Destito, G., Zijlstra, A., Stuhlmann, H., Manchester, M., Lewis, J.D.: Intravital imaging of embryonic and tumor neovasculature using viral nanoparticles. Nat. Protoc. 5, 1406–1417 (2010). https://doi.org/10.1038/nprot.2010.103

    Article  Google Scholar 

  36. Naumenko, V., Van, S., Dastidar, H., Kim, D.-S., Kim, S.-J., Zeng, Z., Deniset, J., Lau, A., Zhang, C., Macia, N., Heyne, B., Jenne, C.N., Mahoney, D.J.: Visualizing oncolytic virus-host interactions in live mice using Intravital microscopy. Mol. Ther. Oncolytics. 10, 14–27 (2018). https://doi.org/10.1016/j.omto.2018.06.001

    Article  Google Scholar 

  37. Denk, W., Strickler, J.H., Webb, W.W.: Two-photon laser scanning fluorescence microscopy. Science. 248, 73–76 (1990). https://doi.org/10.1126/science.2321027

    Article  ADS  Google Scholar 

  38. Benson, R.A., Brewer, J.M., Garside, P.: Visualizing and tracking T cell motility in vivo. Methods Mol. Biol. 1591, 27–41 (2017). https://doi.org/10.1007/978-1-4939-6931-9_3

    Article  Google Scholar 

  39. Cahalan, M.D., Parker, I., Wei, S.H., Miller, M.J.: Two-photon tissue imaging: seeing the immune system in a fresh light. Nat. Rev. Immunol. 2, 872–880 (2002). https://doi.org/10.1038/nri935

    Article  Google Scholar 

  40. Germain, R.N., Castellino, F., Chieppa, M., Egen, J.G., Huang, A.Y.C., Koo, L.Y., Qi, H.: An extended vision for dynamic high-resolution intravital immune imaging. Semin. Immunol. 17, 431–441 (2005). https://doi.org/10.1016/j.smim.2005.09.003

    Article  Google Scholar 

  41. Perrin, L., Bayarmagnai, B., Gligorijevic, B.: Frontiers in intravital multiphoton microscopy of cancer. Cancer Rep., e1192 (2019). https://doi.org/10.1002/cnr2.1192

  42. Brunker, J., Yao, J., Laufer, J., Bohndiek, S.E.: Photoacoustic imaging using genetically encoded reporters: a review. J. Biomed. Opt., 22 (2017). https://doi.org/10.1117/1.JBO.22.7.070901

  43. Hu, S., Wang, L.V.: Photoacoustic imaging and characterization of the microvasculature. J. Biomed. Opt. 15, 011101 (2010). https://doi.org/10.1117/1.3281673

    Article  ADS  Google Scholar 

  44. Valluru, K.S., Willmann, J.K.: Clinical photoacoustic imaging of cancer. Ultrasonography. 35, 267–280 (2016). https://doi.org/10.14366/usg.16035

    Article  Google Scholar 

  45. Valluru, K.S., Wilson, K.E., Willmann, J.K.: Photoacoustic imaging in oncology: translational preclinical and early clinical experience. Radiology. 280, 332–349 (2016). https://doi.org/10.1148/radiol.16151414

    Article  Google Scholar 

  46. van den Berg, P.J., Daoudi, K., Steenbergen, W.: Review of photoacoustic flow imaging: its current state and its promises. Photo-Dermatology. 3, 89–99 (2015). https://doi.org/10.1016/j.pacs.2015.08.001

    Article  Google Scholar 

  47. Robles, F.E., Wilson, C., Grant, G., Wax, A.: Molecular imaging true-colour spectroscopic optical coherence tomography. Nat. Photonics. 5, 744–747 (2011). https://doi.org/10.1038/nphoton.2011.257

    Article  ADS  Google Scholar 

  48. Yin, B., Kuranov, R.V., McElroy, A.B., Kazmi, S., Dunn, A.K., Duong, T.Q., Milner, T.E.: Dual-wavelength photothermal optical coherence tomography for imaging microvasculature blood oxygen saturation. J. Biomed. Opt. 18, 56005 (2013). https://doi.org/10.1117/1.JBO.18.5.056005

    Article  Google Scholar 

  49. Puza, C.J., Warren, W.S., Mosca, P.J.: The changing landscape of dermatology practice: melanoma and pump-probe laser microscopy. Lasers Med. Sci. 32, 1935–1939 (2017). https://doi.org/10.1007/s10103-017-2319-2

    Article  Google Scholar 

  50. Shashkova, S., Leake, M.C.: Single-molecule fluorescence microscopy review: shedding new light on old problems. Biosci. Rep. 37 (2017). https://doi.org/10.1042/BSR20170031

  51. Simpson, M.J., Wilson, J.W., Phipps, M.A., Robles, F.E., Selim, M.A., Warren, W.S.: Nonlinear microscopy of eumelanin and pheomelanin with subcellular resolution. J. Invest. Dermatol. 133, 1822–1826 (2013). https://doi.org/10.1038/jid.2013.37

    Article  Google Scholar 

  52. Kedrin, D., Gligorijevic, B., Wyckoff, J., Verkhusha, V.V., Condeelis, J., Segall, J.E., van Rheenen, J.: Intravital imaging of metastatic behavior through a mammary imaging window. Nat. Methods. 5, 1019–1021 (2008). https://doi.org/10.1038/nmeth.1269

    Article  Google Scholar 

  53. Schafer, R., Leung, H.M., Gmitro, A.F.: Multi-modality imaging of a murine mammary window chamber for breast cancer research. BioTechniques. 57, 45–50 (2014). https://doi.org/10.2144/000114191

    Article  Google Scholar 

  54. Shan, S., Sorg, B., Dewhirst, M.W.: A novel rodent mammary window of orthotopic breast cancer for intravital microscopy. Microvasc. Res. 65, 109–117 (2003). https://doi.org/10.1016/s0026-2862(02)00017-1

    Article  Google Scholar 

  55. Sobolik, T., Su, Y.-J., Ashby, W., Schaffer, D.K., Wells, S., Wikswo, J.P., Zijlstra, A., Richmond, A.: Development of novel murine mammary imaging windows to examine wound healing effects on leukocyte trafficking in mammary tumors with intravital imaging. Intravital. 5 (2016). https://doi.org/10.1080/21659087.2015.1125562

  56. Dorand, R.D., Barkauskas, D.S., Evans, T.A., Petrosiute, A., Huang, A.Y.: Comparison of intravital thinned skull and cranial window approaches to study CNS immunobiology in the mouse cortex. Intravital, 3 (2014). https://doi.org/10.4161/intv.29728

  57. Benbenishty, A., Gadrich, M., Cottarelli, A., Lubart, A., Kain, D., Amer, M., Shaashua, L., Glasner, A., Erez, N., Agalliu, D., Mayo, L., Ben-Eliyahu, S., Blinder, P.: Prophylactic TLR9 stimulation reduces brain metastasis through microglia activation. PLoS Biol. 17 (2019). https://doi.org/10.1371/journal.pbio.2006859

  58. Qiao, S., Qian, Y., Xu, G., Luo, Q., Zhang, Z.: Long-term characterization of activated microglia/macrophages facilitating the development of experimental brain metastasis through intravital microscopic imaging. J. Neuroinflammation. 16, 4 (2019). https://doi.org/10.1186/s12974-018-1389-9

    Article  Google Scholar 

  59. Yuan, H., Wilson, C.M., Xia, J., Doyle, S.L., Li, S., Fales, A.M., Liu, Y., Ozaki, E., Mulfaul, K., Hanna, G., Palmer, G.M., Wang, L.V., Grant, G.A., Vo-Dinh, T.: Plasmonics-enhanced and optically modulated delivery of gold nanostars into brain tumor. Nanoscale. 6, 4078–4082 (2014). https://doi.org/10.1039/c3nr06770j

    Article  ADS  Google Scholar 

  60. Entenberg, D., Voiculescu, S., Guo, P., Borriello, L., Wang, Y., Karagiannis, G.S., Jones, J., Baccay, F., Oktay, M., Condeelis, J.: A permanent window for the murine lung enables high-resolution imaging of cancer metastasis. Nat. Methods. 15, 73–80 (2018). https://doi.org/10.1038/nmeth.4511

    Article  Google Scholar 

  61. Fontanella, A.N., Schroeder, T., Hochman, D.W., Chen, R.E., Hanna, G., Haglund, M.M., Secomb, T.W., Palmer, G.M., Dewhirst, M.W.: Quantitative mapping of hemodynamics in the lung, brain, and dorsal window chamber-grown tumors using a novel, automated algorithm. Microcirculation. 20, 724–735 (2013). https://doi.org/10.1111/micc.12072

    Article  Google Scholar 

  62. Looney, M.R., Bhattacharya, J.: Live imaging of the lung. Annu. Rev. Physiol. 76, 431–445 (2014). https://doi.org/10.1146/annurev-physiol-021113-170331

    Article  Google Scholar 

  63. Babes, L., Kubes, P.: Visualizing the tumor microenvironment of liver metastasis by spinning disk confocal microscopy. Methods Mol. Biol. 1458, 203–215 (2016). https://doi.org/10.1007/978-1-4939-3801-8_15

    Article  Google Scholar 

  64. Benechet, A.P., Ganzer, L., Iannacone, M.: Intravital microscopy analysis of hepatic T cell dynamics. Methods Mol. Biol. 1514, 49–61 (2017). https://doi.org/10.1007/978-1-4939-6548-9_4

    Article  Google Scholar 

  65. Sumen, C., Mempel, T.R., Mazo, I.B., von Andrian, U.H.: Intravital microscopy: visualizing immunity in context. Immunity. 21, 315–329 (2004). https://doi.org/10.1016/j.immuni.2004.08.006

    Article  Google Scholar 

  66. Bentolila, N.Y., Barnhill, R.L., Lugassy, C., Bentolila, L.A.: Intravital imaging of human melanoma cells in the mouse ear skin by two-photon excitation microscopy. Methods Mol. Biol. 1755, 223–232 (2018). https://doi.org/10.1007/978-1-4939-7724-6_15

    Article  Google Scholar 

  67. Chen, B.J., Jiao, Y., Zhang, P., Sun, A.Y., Pitt, G.S., Deoliveira, D., Drago, N., Ye, T., Liu, C., Chao, N.J.: Long-term in vivo imaging of multiple organs at the single cell level. PLoS One. 8, e52087 (2013). https://doi.org/10.1371/journal.pone.0052087

    Article  ADS  Google Scholar 

  68. Güç, E., Fankhauser, M., Lund, A.W., Swartz, M.A., Kilarski, W.W.: Long-term intravital immunofluorescence imaging of tissue matrix components with epifluorescence and two-photon microscopy. J. Vis. Exp. (2014). https://doi.org/10.3791/51388

  69. Birer, S.R., Lee, C.-T., Choudhury, K.R., Young, K.H., Spasojevic, I., Batinic-Haberle, I., Crapo, J.D., Dewhirst, M.W., Ashcraft, K.A.: Inhibition of the continuum of radiation-induced normal tissue injury by a redox-active Mn porphyrin. Radiat. Res. 188, 94–104 (2017). https://doi.org/10.1667/RR14757.1.S1

    Article  ADS  Google Scholar 

  70. Dähn, S., Schwalbach, P., Maksan, S., Wöhleke, F., Benner, A., Kuntz, C.: Influence of different gases used for laparoscopy (helium, carbon dioxide, room air, and xenon) on tumor volume, histomorphology, and leukocyte-tumor-endothelium interaction in intravital microscopy. Surg. Endosc. 19, 65–70 (2005). https://doi.org/10.1007/s00464-003-9298-z

    Article  Google Scholar 

  71. Metildi, C.A., Tang, C.-M., Kaushal, S., Leonard, S.Y., Magistri, P., Tran Cao, H.S., Hoffman, R.M., Bouvet, M., Sicklick, J.K.: In vivo fluorescence imaging of gastrointestinal stromal tumors using fluorophore-conjugated anti-KIT antibody. Ann. Surg. Oncol. 20(Suppl 3), S693–S700 (2013). https://doi.org/10.1245/s10434-013-3172-6

    Article  Google Scholar 

  72. Oh, G., Yoo, S.W., Jung, Y., Ryu, Y.-M., Park, Y., Kim, S.-Y., Kim, K.H., Kim, S., Myung, S.-J., Chung, E.: Intravital imaging of mouse colonic adenoma using MMP-based molecular probes with multi-channel fluorescence endoscopy. Biomed. Opt. Express. 5, 1677–1689 (2014). https://doi.org/10.1364/BOE.5.001677

    Article  Google Scholar 

  73. Realdon, S., Dassie, E., Fassan, M., Dall’Olmo, L., Hatem, G., Buda, A., Arcidiacono, D., Diamantis, G., Zhang, H., Greene, M.I., Sturniolo, G.C., Rugge, M., Alberti, A., Battaglia, G.: In vivo molecular imaging of HER2 expression in a rat model of Barrett’s esophagus adenocarcinoma. Dis. Esophagus. 28, 394–403 (2015). https://doi.org/10.1111/dote.12210

    Article  Google Scholar 

  74. Jung, S., Aliberti, J., Graemmel, P., Sunshine, M.J., Kreutzberg, G.W., Sher, A., Littman, D.R.: Analysis of fractalkine receptor CX(3)CR1 function by targeted deletion and green fluorescent protein reporter gene insertion. Mol. Cell. Biol. 20, 4106–4114 (2000). https://doi.org/10.1128/mcb.20.11.4106-4114.2000

    Article  Google Scholar 

  75. Rua, R., McGavern, D.B.: Elucidation of monocyte/macrophage dynamics and function by intravital imaging. J. Leukoc. Biol. 98, 319–332 (2015). https://doi.org/10.1189/jlb.4RI0115-006RR

    Article  Google Scholar 

  76. Hasenberg, A., Hasenberg, M., Männ, L., Neumann, F., Borkenstein, L., Stecher, M., Kraus, A., Engel, D.R., Klingberg, A., Seddigh, P., Abdullah, Z., Klebow, S., Engelmann, S., Reinhold, A., Brandau, S., Seeling, M., Waisman, A., Schraven, B., Göthert, J.R., Nimmerjahn, F., Gunzer, M.: Catchup: a mouse model for imaging-based tracking and modulation of neutrophil granulocytes. Nat. Methods. 12, 445–452 (2015). https://doi.org/10.1038/nmeth.3322

    Article  Google Scholar 

  77. Heymann, F., Niemietz, P.M., Peusquens, J., Ergen, C., Kohlhepp, M., Mossanen, J.C., Schneider, C., Vogt, M., Tolba, R.H., Trautwein, C., Martin, C., Tacke, F.: Long term intravital multiphoton microscopy imaging of immune cells in healthy and diseased liver using CXCR6.Gfp reporter mice. J. Vis. Exp. (2015). https://doi.org/10.3791/52607

  78. Shapovalova, M., Pyper, S.R., Moriarity, B.S., LeBeau, A.M.: The molecular imaging of natural killer cells. Mol. Imaging. 17 (2018). https://doi.org/10.1177/1536012118794816

  79. Oghumu, S., Dong, R., Varikuti, S., Shawler, T., Kampfrath, T., Terrazas, C.A., Lezama-Davila, C., Ahmer, B.M.M., Whitacre, C.C., Rajagopalan, S., Locksley, R., Sharpe, A.H., Satoskar, A.R.: Distinct populations of innate CD8+ T cells revealed in a CXCR3 reporter mouse. J. Immunol. 190, 2229–2240 (2013). https://doi.org/10.4049/jimmunol.1201170

    Article  Google Scholar 

  80. Lindquist, R.L., Shakhar, G., Dudziak, D., Wardemann, H., Eisenreich, T., Dustin, M.L., Nussenzweig, M.C.: Visualizing dendritic cell networks in vivo. Nat. Immunol. 5, 1243–1250 (2004). https://doi.org/10.1038/ni1139

    Article  Google Scholar 

  81. Tal, O., Lim, H.Y., Gurevich, I., Milo, I., Shipony, Z., Ng, L.G., Angeli, V., Shakhar, G.: DC mobilization from the skin requires docking to immobilized CCL21 on lymphatic endothelium and intralymphatic crawling. J. Exp. Med. 208, 2141–2153 (2011). https://doi.org/10.1084/jem.20102392

    Article  Google Scholar 

  82. Dubey, P.: Reporter gene imaging of immune responses to cancer: progress and challenges. Theranostics. 2, 355–362 (2012). https://doi.org/10.7150/thno.3903

    Article  Google Scholar 

  83. Li, M., Wang, Y., Liu, M., Lan, X.: Multimodality reporter gene imaging: construction strategies and application. Theranostics. 8, 2954–2973 (2018b). https://doi.org/10.7150/thno.24108

    Article  Google Scholar 

  84. Li, S., Chen, L.-X., Peng, X.-H., Wang, C., Qin, B.-Y., Tan, D., Han, C.-X., Yang, H., Ren, X.-N., Liu, F., Xu, C.-H., Zhou, X.-H.: Overview of the reporter genes and reporter mouse models. Animal Model Exp. Med. 1, 29–35 (2018c). https://doi.org/10.1002/ame2.12008

    Article  Google Scholar 

  85. Qie, Y., Yuan, H., von Roemeling, C.A., Chen, Y., Liu, X., Shih, K.D., Knight, J.A., Tun, H.W., Wharen, R.E., Jiang, W., Kim, B.Y.S.: Surface modification of nanoparticles enables selective evasion of phagocytic clearance by distinct macrophage phenotypes. Sci. Rep. 6 (2016). https://doi.org/10.1038/srep26269

  86. Chen, Z., Feng, X., Herting, C.J., Garcia, V.A., Nie, K., Pong, W.W., Rasmussen, R., Dwivedi, B., Seby, S., Wolf, S.A., Gutmann, D.H., Hambardzumyan, D.: Cellular and molecular identity of tumor-associated macrophages in glioblastoma. Cancer Res. 77, 2266–2278 (2017). https://doi.org/10.1158/0008-5472.CAN-16-2310

    Article  Google Scholar 

  87. Rabinovich, B.A., Radu, C.G.: Imaging adoptive cell transfer based cancer immunotherapy. Curr. Pharm. Biotechnol. 11, 672–684 (2010). https://doi.org/10.2174/138920110792246528

    Article  Google Scholar 

  88. Ansari, A.M., Ahmed, A.K., Matsangos, A.E., Lay, F., Born, L.J., Marti, G., Harmon, J.W., Sun, Z.: Cellular GFP toxicity and immunogenicity: potential confounders in in vivo cell tracking experiments. Stem Cell Rev. 12, 553–559 (2016). https://doi.org/10.1007/s12015-016-9670-8

    Article  Google Scholar 

  89. Miller, M.J., Wei, S.H., Parker, I., Cahalan, M.D.: Two-photon imaging of lymphocyte motility and antigen response in intact lymph node. Science. 296, 1869–1873 (2002). https://doi.org/10.1126/science.1070051

    Article  ADS  Google Scholar 

  90. Coisne, C., Lyck, R., Engelhardt, B.: Live cell imaging techniques to study T cell trafficking across the blood-brain barrier in vitro and in vivo. Fluids Barriers CNS. 10, 7 (2013). https://doi.org/10.1186/2045-8118-10-7

    Article  Google Scholar 

  91. Lee, H.W., Gangadaran, P., Kalimuthu, S., Ahn, B.-C.: Advances in molecular imaging strategies for in vivo tracking of immune cells [WWW document]. Biomed. Res. Int. (2016). https://doi.org/10.1155/2016/1946585

  92. Liu, Y., Huang, W., Xiong, C., Huang, Y., Chen, B.J., Racioppi, L., Chao, N., Vo-Dinh, T.: Biodistribution and sensitive tracking of immune cells with plasmonic gold nanostars. Int. J. Nanomedicine. 14, 3403–3411 (2019). https://doi.org/10.2147/IJN.S192189

    Article  Google Scholar 

  93. Kilarski, W.W., Güç, E., Teo, J.C.M., Oliver, S.R., Lund, A.W., Swartz, M.A.: Intravital immunofluorescence for visualizing the microcirculatory and immune microenvironments in the mouse ear dermis. PLoS One. 8, e57135 (2013). https://doi.org/10.1371/journal.pone.0057135

    Article  ADS  Google Scholar 

  94. Egeblad, M., Ewald, A.J., Askautrud, H.A., Truitt, M.L., Welm, B.E., Bainbridge, E., Peeters, G., Krummel, M.F., Werb, Z.: Visualizing stromal cell dynamics in different tumor microenvironments by spinning disk confocal microscopy. Dis. Model. Mech. 1, 155–167 (2008). https://doi.org/10.1242/dmm.000596

    Article  Google Scholar 

  95. Ramamonjisoa, N., Ackerstaff, E.: Characterization of the tumor microenvironment and tumor-stroma interaction by non-invasive preclinical imaging. Front. Oncol. 7, 3 (2017). https://doi.org/10.3389/fonc.2017.00003

    Article  Google Scholar 

  96. Conway, J.R.W., Warren, S.C., Timpson, P.: Context-dependent intravital imaging of therapeutic response using intramolecular FRET biosensors. Methods. 128, 78–94 (2017). https://doi.org/10.1016/j.ymeth.2017.04.014

    Article  Google Scholar 

  97. Smith, B.A., Smith, B.D.: Biomarkers and molecular probes for cell death imaging and targeted therapeutics. Bioconjug. Chem. 23, 1989–2006 (2012). https://doi.org/10.1021/bc3003309

    Article  Google Scholar 

  98. Zeng, W., Wang, X., Xu, P., Liu, G., Eden, H.S., Chen, X.: Molecular imaging of apoptosis: from micro to macro. Theranostics. 5, 559–582 (2015). https://doi.org/10.7150/thno.11548

    Article  Google Scholar 

  99. Chitneni, S.K., Palmer, G.M., Zalutsky, M.R., Dewhirst, M.W.: Molecular imaging of hypoxia. J. Nucl. Med. 52, 165–168 (2011). https://doi.org/10.2967/jnumed.110.075663

    Article  Google Scholar 

  100. Dewhirst, M.W., Cao, Y., Moeller, B.: Cycling hypoxia and free radicals regulate angiogenesis and radiotherapy response. Nat. Rev. Cancer. 8, 425–437 (2008). https://doi.org/10.1038/nrc2397

    Article  Google Scholar 

  101. Pogue, B.W., Feng, J., LaRochelle, E.P., Bruža, P., Lin, H., Zhang, R., Shell, J.R., Dehghani, H., Davis, S.C., Vinogradov, S.A., Gladstone, D.J., Jarvis, L.A.: Maps of in vivo oxygen pressure with submillimetre resolution and nanomolar sensitivity enabled by Cherenkov-excited luminescence scanned imaging. Nat. Biomed. Eng. 2, 254–264 (2018). https://doi.org/10.1038/s41551-018-0220-3

    Article  Google Scholar 

  102. Wolfbeis, O.S.: Luminescent sensing and imaging of oxygen: fierce competition to the Clark electrode. BioEssays. 37, 921–928 (2015). https://doi.org/10.1002/bies.201500002

    Article  Google Scholar 

  103. Zhang, G., Palmer, G.M., Dewhirst, M.W., Fraser, C.L.: A dual-emissive-materials design concept enables tumour hypoxia imaging. Nat. Mater. 8, 747–751 (2009). https://doi.org/10.1038/nmat2509

    Article  ADS  Google Scholar 

  104. Rytelewski, M., Haryutyunan, K., Nwajei, F., Shanmugasundaram, M., Wspanialy, P., Zal, M.A., Chen, C.-H., El Khatib, M., Plunkett, S., Vinogradov, S.A., Konopleva, M., Zal, T.: Merger of dynamic two-photon and phosphorescence lifetime microscopy reveals dependence of lymphocyte motility on oxygen in solid and hematological tumors. J. Immunother. Cancer. 7, 78 (2019). https://doi.org/10.1186/s40425-019-0543-y

    Article  Google Scholar 

  105. Chen, M., Chen, M., Knox, H.J., Knox, H.J., Tang, Y., Liu, W., Nie, L., Nie, L., Chan, J., Chan, J., Chan, J., Yao, J., Yao, J.: Simultaneous photoacoustic imaging of intravascular and tissue oxygenation. Opt. Lett. OL 44, 3773–3776 (2019). https://doi.org/10.1364/OL.44.003773

    Article  ADS  Google Scholar 

  106. Rickard, A.G., Palmer, G.M., Dewhirst, M.W.: Clinical and pre-clinical methods for quantifying tumor hypoxia. Adv. Exp. Med. Biol. 1136, 19–41 (2019). https://doi.org/10.1007/978-3-030-12734-3_2

    Article  Google Scholar 

  107. Lee, J.A., Kozikowski, R.T., Sorg, B.S.: In vivo microscopy of microvessel oxygenation and network connections. Microvasc. Res. 98, 29–39 (2015). https://doi.org/10.1016/j.mvr.2014.11.007

    Article  Google Scholar 

  108. Shonat, R.D., Wachman, E.S., Niu, W., Koretsky, A.P., Farkas, D.L.: Near-simultaneous hemoglobin saturation and oxygen tension maps in mouse brain using an AOTF microscope. Biophys. J. 73, 1223–1231 (1997). https://doi.org/10.1016/S0006-3495(97)78155-4

    Article  Google Scholar 

  109. Wachman, E.S., Niu, W., Farkas, D.L.: AOTF microscope for imaging with increased speed and spectral versatility. Biophys. J. 73, 1215–1222 (1997). https://doi.org/10.1016/S0006-3495(97)78154-2

    Article  Google Scholar 

  110. Tzoumas, S., Ntziachristos, V.: Spectral unmixing techniques for optoacoustic imaging of tissue pathophysiology. Philos. Trans. A Math. Phys. Eng. Sci. 375 (2017). https://doi.org/10.1098/rsta.2017.0262

  111. Tomura, M., Yoshida, N., Tanaka, J., Karasawa, S., Miwa, Y., Miyawaki, A., Kanagawa, O.: Monitoring cellular movement in vivo with photoconvertible fluorescence protein “Kaede” transgenic mice. Proc. Natl. Acad. Sci. U. S. A. 105, 10871–10876 (2008). https://doi.org/10.1073/pnas.0802278105

    Article  ADS  Google Scholar 

  112. Li, L., Shemetov, A.A., Baloban, M., Hu, P., Zhu, L., Shcherbakova, D.M., Zhang, R., Shi, J., Yao, J., Wang, L.V., Verkhusha, V.V.: Small near-infrared photochromic protein for photoacoustic multi-contrast imaging and detection of protein interactions in vivo. Nat. Commun. 9, 2734 (2018a). https://doi.org/10.1038/s41467-018-05231-3

    Article  ADS  Google Scholar 

  113. Chen-Bee, C.H., Agoncillo, T., Lay, C.C., Frostig, R.D.: Intrinsic signal optical imaging of brain function using short stimulus delivery intervals. J. Neurosci. Methods. 187, 171–182 (2010). https://doi.org/10.1016/j.jneumeth.2010.01.009

    Article  Google Scholar 

  114. Haglund, M.M., Ojemann, G.A., Hochman, D.W.: Optical imaging of epileptiform and functional activity in human cerebral cortex. Nature. 358, 668–671 (1992). https://doi.org/10.1038/358668a0

    Article  ADS  Google Scholar 

  115. Dirkx, A.E.M., Oude Egbrink, M.G.A., Kuijpers, M.J.E., van der Niet, S.T., Heijnen, V.V.T., Bouma-ter Steege, J.C.A., Wagstaff, J., Griffioen, A.W.: Tumor angiogenesis modulates leukocyte-vessel wall interactions in vivo by reducing endothelial adhesion molecule expression. Cancer Res. 63, 2322–2329 (2003)

    Google Scholar 

  116. Dreher, M.R., Liu, W., Michelich, C.R., Dewhirst, M.W., Yuan, F., Chilkoti, A.: Tumor vascular permeability, accumulation, and penetration of macromolecular drug carriers. J. Natl. Cancer Inst. 98, 335–344 (2006). https://doi.org/10.1093/jnci/djj070

    Article  Google Scholar 

  117. Larina, I.V., Shen, W., Kelly, O.G., Hadjantonakis, A.-K., Baron, M.H., Dickinson, M.E.: A membrane associated mCherry fluorescent reporter line for studying vascular remodeling and cardiac function during murine embryonic development. Anat. Rec. (Hoboken). 292, 333–341 (2009). https://doi.org/10.1002/ar.20821

    Article  Google Scholar 

  118. Manzoor, A.A., Lindner, L.H., Landon, C.D., Park, J.-Y., Simnick, A.J., Dreher, M.R., Das, S., Hanna, G., Park, W., Chilkoti, A., Koning, G.A., ten Hagen, T.L.M., Needham, D., Dewhirst, M.W.: Overcoming limitations in nanoparticle drug delivery: triggered, intravascular release to improve drug penetration into tumors. Cancer Res. 72, 5566–5575 (2012). https://doi.org/10.1158/0008-5472.CAN-12-1683

    Article  Google Scholar 

  119. Zhu, J., Dugas-Ford, J., Chang, M., Purta, P., Han, K.-Y., Hong, Y.-K., Dickinson, M.E., Rosenblatt, M.I., Chang, J.-H., Azar, D.T.: Simultaneous in vivo imaging of blood and lymphatic vessel growth in Prox1-GFP/Flk1::myr-mCherry mice. FEBS J. 282, 1458–1467 (2015). https://doi.org/10.1111/febs.13234

    Article  Google Scholar 

  120. Hägerling, R., Pollmann, C., Kremer, L., Andresen, V., Kiefer, F.: Intravital two-photon microscopy of lymphatic vessel development and function using a transgenic Prox1 promoter-directed mOrange2 reporter mouse. Biochem. Soc. Trans. 39, 1674–1681 (2011). https://doi.org/10.1042/BST20110722

    Article  Google Scholar 

  121. Truman, L.A., Bentley, K.L., Smith, E.C., Massaro, S.A., Gonzalez, D.G., Haberman, A.M., Hill, M., Jones, D., Min, W., Krause, D.S., Ruddle, N.H.: ProxTom lymphatic vessel reporter mice reveal Prox1 expression in the adrenal medulla, megakaryocytes, and platelets. Am. J. Pathol. 180, 1715–1725 (2012). https://doi.org/10.1016/j.ajpath.2011.12.026

    Article  Google Scholar 

  122. Monsky, W.L., Fukumura, D., Gohongi, T., Ancukiewcz, M., Weich, H.A., Torchilin, V.P., Yuan, F., Jain, R.K.: Augmentation of transvascular transport of macromolecules and nanoparticles in tumors using vascular endothelial growth factor. Cancer Res. 59, 4129–4135 (1999)

    Google Scholar 

  123. Kai, M.P., Brighton, H.E., Fromen, C.A., Shen, T.W., Luft, J.C., Luft, Y.E., Keeler, A.W., Robbins, G.R., Ting, J.P.Y., Zamboni, W.C., Bear, J.E., DeSimone, J.M.: Tumor presence induces global immune changes and enhances nanoparticle clearance. ACS Nano. 10, 861–870 (2016). https://doi.org/10.1021/acsnano.5b05999

    Article  Google Scholar 

  124. Park, K.: Impact of anti-PEG antibodies on PEGylated nanoparticles fate in vivo. J. Control. Release. 287, 257 (2018). https://doi.org/10.1016/j.jconrel.2018.09.014

    Article  Google Scholar 

  125. Zhang, P., Sun, F., Liu, S., Jiang, S.: Anti-PEG antibodies in the clinic: current issues and beyond PEGylation. J. Control. Release. 244, 184–193 (2016). https://doi.org/10.1016/j.jconrel.2016.06.040

    Article  Google Scholar 

  126. Shukla, S., Dorand, R.D., Myers, J.T., Woods, S.E., Gulati, N.M., Stewart, P.L., Commandeur, U., Huang, A.Y., Steinmetz, N.F.: Multiple administrations of viral nanoparticles alter in vivo behavior-insights from intravital microscopy. ACS Biomater Sci. Eng. 2, 829–837 (2016). https://doi.org/10.1021/acsbiomaterials.6b00060

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Radiation Oncology, Duke University Medical Center, Durham, NC, USA

    Gregory M. Palmer

  2. Duke University School of Medicine, Durham, NC, USA

    Yuxiang Wang & Antoine Mansourati

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    Tuan Vo-Dinh

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Palmer, G.M., Wang, Y., Mansourati, A. (2021). Intravital Optical Imaging to Monitor Anti-Tumor Immunological Response in Preclinical Models. In: Vo-Dinh, T. (eds) Nanoparticle-Mediated Immunotherapy. Bioanalysis, vol 12. Springer, Cham. https://doi.org/10.1007/978-3-030-78338-9_4

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