Abstract
Cancer immunotherapies, particularly immune-checkpoint blockade and T cell-based adoptive cell therapy, have recently been recognized as cancer treatments that show strong and durable responses even for advanced cancer patients with multiple metastases. The major issues in the development of cancer immunotherapy are the identification of biomarkers to distinguish responders and non-responders, and the improvement of efficacy of immunotherapy possibly by combination with appropriate immune interventions targeting different key regulating points in the anti-tumor immune responses. Interestingly, pretreatment T cell immune status varies among cancer patients, and appears to correlate with responses to various cancer treatments including surgery, chemotherapy, radiation therapy, and immunotherapy. Balance of anti-tumor T cell induction pathway and immunosuppressive pathway, which are regulated by characteristics of both cancer cells and patients’ immune reactivity, may define the differential immune status among cancer patients along with environmental factors such as intestinal microbiota. The analysis of such mechanisms may lead to the identification of immune biomarkers and immune-modulating strategies for combination immunotherapies. Further research on human cancer immunopathology will lead to the development of effective personalized combination immunotherapies based on the evaluation of cancer patients’ immune status.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Bindea G, Mlecnik B, Tosolini M et al (2013) Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer. Immunity 39:782–795
Brahmer JR, Tykodi SS, Chow LQ et al (2012) Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 366:2455–2465
Fridman WH, Pagès F, Sautès-Fridman C et al (2012) The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer 12:298–306
Galon J, Mlecnik B, Bindea G et al (2014) Towards the introduction of the ‘Immunoscore’ in the classification of malignant tumours. J Pathol 232(2):199–209
Hodi FS, O’Day SJ, McDermott DF et al (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363:711–723
Ishikawa T, Fujita T, Suzuki Y et al (2003) Tumor-specific immunological recognition of frameshift-mutated peptides in colon cancer with microsatellite instability. Cancer Res 63:5564–5572
Iwata-Kajihara T, Sumimoto H et al (2011) Enhanced cancer immunotherapy using STAT3-depleted dendritic cells with high Th1-inducing ability and resistance to cancer cell-derived inhibitory factors. J Immunol 187:27–36
Kalos M, Levine BL, Porter DL et al (2011) T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Sci Transl Med 3:95
Kawakami Y, Eliyahu S, Delgado CH et al (1994a) Cloning of the gene coding for a shared human melanoma antigen recognized by autologous T cells infiltrating into tumor. Proc Natl Acad Sci U S A 91:3515–3519
Kawakami Y, Eliyahu S, Delgado CH et al (1994b) Identification of human melanoma antigen recognized by tumor infiltrating lymphocytes associated with in vivo tumor rejection. Proc Natl Acad Sci U S A 91:6458–6462
Kawakami Y, Eliyahu S, Sakaguchi K et al (1994c) Identification of the immunodominant peptides of the MART-1 human melanoma antigen recognized by the majority of HLA-A2 restricted tumor infiltrating lymphocytes. J Exp Med 180:347–352
Kawakami Y, Wang X, Shofuda T et al (2001) Isolation of a new melanoma antigen, MART-2, containing a mutated epitope recognized by autologous tumor infiltrating T lymphocytes. J Immunol 166:2871–2877
Kawakami Y, Yaguchi T, Sumimoto H et al (2013a) Roles of signaling pathways in cancer cells and immune cells in generation of immunosuppressive tumor-associated microenvironments. In: Shurin M, Malyguine A, Umansky V (eds) Tumor immunoenvironment. Dordrecht/Heidelberg/New York/London
Kawakami Y, Yaguchi T, Sumimoto H et al (2013b) Improvement of cancer immunotherapy by combining molecular targeted therapy. Front Oncol 3:136
Kudo-Saito C, Shirako H, Takeuchi T et al (2009) Cancer metastasis is accelerated through immunosuppression during EMT of cancer cell. Cancer Cell 16:195–206
Kudo-Saito C, Shirako H, Ohike M et al (2012) CCL2 is critical for immunosuppression to promote cancer metastasis. Clin Exp Metastasis 30:393–405
Mlecnik B, Bindea G, Angell HK et al (2014) Functional network pipeline reveals genetic determinants associated with in situ lymphocyte proliferation and survival of cancer patients. Sci Transl Med 6:228
Nakamura S, Yaguchi T, Kawamura N et al (2014) TGF-β1 in tumor microenvironments induces immunosuppression in the tumors and sentinel lymph nodes and promotes tumor progression. J Immunother 37:63–72
Nishio H, Yaguchi T, Sugiyama J et al (2014) Immunosuppression through constitutively activated NF-κB signaling in human ovarian cancer and its reversal by a NF-κB inhibitor. Br J Cancer 110:2965–2974
Ohkusu-Tsukada K, Ohta S, Kawakami Y et al (2011) Adjuvant effects of formalin-inactivated HSV through activation of dendritic cells and inactivation of myeloid-derived suppressor cells in cancer immunotherapy. Int J Cancer 128:119–131
Pagès F, Kirilovsky A, Mlecnik B et al (2009) In situ cytotoxic and memory T cells predict outcome in patients with early-stage colorectal cancer. J Clin Oncol 27:5944–5951
Robbins PF, El-Gamil M, Li YF et al (1996) A mutated b2-catenin gene encodes a melanoma – specific antigen recognized by tumor infiltrating lymphocytes. J Exp Med 183:1185–1192
Robbins PF, Morgan RA, Feldman SA et al (2011) Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1. J Clin Oncol 29:917–924
Robbins PF, Lu YC, El-Gamil M et al (2013) Mining exomic sequencing data to identify mutated antigens recognized by adoptively transferred tumor-reactive T cells. Nat Med 19:747–752
Rosenberg SA, Yang J, Schwartzentruber D et al (1998) Immunologic and therapeutic evaluation of a synthetic peptide vaccine for the treatment of patients with metastatic melanoma. Nat Med 4:321–327
Rosenberg SA, Yang JC, Sherry RM et al (2011) Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy. Clin Cancer Res 17:4550–4557
Salgaller M, Marincola F, Rivoltini L et al (1995) Recognition of multiple epitopes in the human melanoma antigen gp100 by antigen specific peripheral blood lymphocytes stimulated with synthetic peptides. Cancer Res 55:4972–4979
Schreiber RD et al (2011) Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science 331:1565–1570
Sumimoto H, Imabayashi F, Iwata T et al (2006) The BRAF-MAPK signaling pathway is essential for cancer immune evasion in human melanoma cells. J Exp Med 203:1651–1656
Taube JM, Anders RA, Young GD et al (2014) Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Sci Transl Med 4:127
Toda M, Iizuka Y, Kawase T et al (2002) Immuno-viral therapy of brain tumors by combination of viral therapy with cancer vaccination using a replication-conditional HSV. Cancer Gene Ther 9:356–364
Topalian SL, Hodi FS, Brahmer JR et al (2013) Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 366:2443–2454
Udagawa M, Kudo-Saito C, Hasegawa G et al (2006) Enhancement of immunologic tumor regression by intratumoral administration of dendritic cells in combination with cryoablative tumor pretreatment and Bacillus Calmette-Guerin cell wall skeleton stimulation. Clin Cancer Res 12:7465–7475
Ueda R, Iizuka Y, Yoshida K, Kawase T, Kawakami Y, Toda M (2004) Identification of a human glioma antigen, SOX6, recognized by patients’ sera. Oncogene 23:1420–1427
Ueda R, Ohkusu-Tsukada K, Fusaki N et al (2010) Identification of HLA-A2- and A24-restricted T-cell epitopes derived from SOX6 expressed in glioma stem cells for immunotherapy. Int J Cancer 126:919–929
Wagle N, Emery C, Berger MF et al (2011) Dissecting therapeutic resistance to RAF inhibition in melanoma by tumor genomic profiling. J Clin Oncol 29:3085–3096
Wilmott JS, Long GV, Howle JR et al (2012) Selective BRAF inhibitors induce marked T-cell infiltration into human metastatic melanoma. Clin Cancer Res 18:1386–1394
Yaguchi T, Sumimoto H, Kudo-Saito C, Tsukamoto N, Ueda R, Iwata-Kajihara T, Nishio H, Kawamura N, Kawakami Y et al (2011) The mechanisms of cancer immunoescape and development of overcoming strategies. Int J Hematol 93:294
Yaguchi T, Goto Y, Kido K, Mochimaru H et al (2012) Immune suppression and resistance mediated by constitutive activation of Wnt/β-catenin signaling in human melanoma cells. J Immunol 189:2110–2117
Acknowledgments
These studies were supported by Grants-in-Aid for Scientific Research (23240128, 26221005) from the Japan Society for Promotion of Science, a research program of the Project for Development of Innovative Research on Cancer Therapeutics (P-Direct) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and a Grant-in-Aid for Cancer Research (23-A-22, 19–14) from the Ministry of Health, Labour, and Welfare, Japan. We also thank Ms. Misako Sakamoto and Ms. Ryoko Suzuki for technical support and editorial assistance.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer Japan
About this chapter
Cite this chapter
Kawakami, Y. et al. (2015). Development of Personalized Combination Cancer Immunotherapy Based on the Patients’ Immune Status. In: Seya, T., Matsumoto, M., Udaka, K., Sato, N. (eds) Inflammation and Immunity in Cancer. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55327-4_20
Download citation
DOI: https://doi.org/10.1007/978-4-431-55327-4_20
Publisher Name: Springer, Tokyo
Print ISBN: 978-4-431-55326-7
Online ISBN: 978-4-431-55327-4
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)