Abstract
Mucosal-associated invariant T (MAIT) cell infiltration has been demonstrated in colorectal and hepatocellular carcinoma, and their ability to produce Th1- and Th17-associated cytokines, as well as their cytotoxic function, suggests that MAIT cells may have important functions in both reducing and promoting protective tumor immunity. Here, we describe enzymatic methods to isolate intraepithelial and lamina propria lymphocyte single cell suspensions from colon tissue and tumors containing viable MAIT cells, which can be used for further purification, flow cytometry analysis, or culture.
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References
Dias J, Boulouis C, Sobkowiak MJ, Lal KG, Emgard J, Buggert M, Parrot T, Gorin JB, Leeansyah E, Sandberg JK (2018) Factors influencing functional heterogeneity in human mucosa-associated invariant T cells. Front Immunol 9:1602. https://doi.org/10.3389/fimmu.2018.01602
Gherardin NA, Souter MN, Koay HF, Mangas KM, Seemann T, Stinear TP, Eckle SB, Berzins SP, d’Udekem Y, Konstantinov IE, Fairlie DP, Ritchie DS, Neeson PJ, Pellicci DG, Uldrich AP, McCluskey J, Godfrey DI (2018) Human blood MAIT cell subsets defined using MR1 tetramers. Immunol Cell Biol 96(5):507–525. https://doi.org/10.1111/imcb.12021
Gherardin NA, Keller AN, Woolley RE, Le Nours J, Ritchie DS, Neeson PJ, Birkinshaw RW, Eckle SBG, Waddington JN, Liu L, Fairlie DP, Uldrich AP, Pellicci DG, McCluskey J, Godfrey DI, Rossjohn J (2016) Diversity of T cells restricted by the MHC class I-related molecule MR1 facilitates differential antigen recognition. Immunity 44(1):32–45
Dias J, Boulouis C, Gorin JB, van den Biggelaar R, Lal KG, Gibbs A, Loh L, Gulam MY, Sia WR, Bari S, Hwang WYK, Nixon DF, Nguyen S, Betts MR, Buggert M, Eller MA, Broliden K, Tjernlund A, Sandberg JK, Leeansyah E (2018) The CD4(−)CD8(−) MAIT cell subpopulation is a functionally distinct subset developmentally related to the main CD8(+) MAIT cell pool. Proc Natl Acad Sci U S A 115(49):E11513–E11522. https://doi.org/10.1073/pnas.1812273115
Sundstrom P, Ahlmanner F, Akeus P, Sundquist M, Alsen S, Yrlid U, Borjesson L, Sjoling A, Gustavsson B, Wong SBJ, Quiding-Jarbrink M (2015) Human mucosa-associated invariant T cells accumulate in Colon adenocarcinomas but produce reduced amounts of IFN-gamma. J Immunol 195(7):3472–3481. https://doi.org/10.4049/jimmunol.1500258
Zabijak L, Attencourt C, Guignant C, Chatelain D, Marcelo P, Marolleau JP, Treiner E (2015) Increased tumor infiltration by mucosal-associated invariant T cells correlates with poor survival in colorectal cancer patients. Cancer Immunol Immun 64(12):1601–1608. https://doi.org/10.1007/s00262-015-1764-7
Won EJ, Ju JK, Cho YN, Jin HM, Park KJ, Kim TJ, Kwon YS, Kee HJ, Kim JC, Kee SJ, Park YW (2016) Clinical relevance of circulating mucosal-associated invariant T cell levels and their anti-cancer activity in patients with mucosal-associated cancer. Oncotarget 7(46):76274–76290. https://doi.org/10.18632/oncotarget.11187
Ling LM, Lin YY, Zheng WW, Hong S, Tang XQ, Zhao PW, Li M, Ni JS, Li CG, Wang L, Jiang YF (2016) Circulating and tumor-infiltrating mucosal associated invariant T (MAIT) cells in colorectal cancer patients. Sci Rep-UK 6:ARTN 20358, https://doi.org/10.1038/srep20358
Gherardin NA, Loh L, Admojo L, Davenport AJ, Richardson K, Rogers A, Darcy PK, Jenkins MR, Prince HM, Harrison SJ, Quach H, Fairlie DP, Kedzierska K, McCluskey J, Uldrich AP, Neeson PJ, Ritchie DS, Godfrey DI (2018) Enumeration, functional responses and cytotoxic capacity of MAIT cells in newly diagnosed and relapsed multiple myeloma. Sci Rep 8(1):4159. https://doi.org/10.1038/s41598-018-22130-1
Duan M, Goswami S, Shi JY, Wu LJ, Wang XY, Ma JQ, Zhang Z, Shi Y, Ma LJ, Zhang S, Xi R, Cao Y, Zhou J, Fan J, Zhang XM, Gao Q (2019) Activated and exhausted MAIT cells foster disease progression and indicate poor outcome in hepatocellular carcinoma. Clin Cancer Res. https://doi.org/10.1158/1078-0432.CCR-18-3040
Shaler CR, Tun-Abraham ME, Skaro AI, Khazaie K, Corbett AJ, Mele T, Hernandez-Alejandro R, Haeryfar SMM (2017) Mucosa-associated invariant T cells infiltrate hepatic metastases in patients with colorectal carcinoma but are rendered dysfunctional within and adjacent to tumor microenvironment. Cancer Immunol Immunother. https://doi.org/10.1007/s00262-017-2050-7
Peterfalvi A, Gomori E, Magyarlaki T, Pal J, Banati M, Javorhazy A, Szekeres-Bartho J, Szereday L, Illes Z (2008) Invariant Valpha7.2-Jalpha33 TCR is expressed in human kidney and brain tumors indicating infiltration by mucosal-associated invariant T (MAIT) cells. Int Immunol 20(12):1517–1525. https://doi.org/10.1093/intimm/dxn111
Sundström P et al (2019) Tumor-infiltrating mucosal-associated invariant T (MAIT) cells retain expression of cytotoxic effector molecules. Oncotarget 10(29):2810–2823. https://doi.org/10.18632/oncotarget.26866
Acknowledgment
This work was supported by the Swedish Research Council and the Swedish Cancer Foundation.
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Rodin, W., Sundström, P., Quiding Järbrink, M. (2020). Isolation and Characterization of MAIT Cells from Tumor Tissues. In: Kaipe, H., Magalhaes, I. (eds) MAIT Cells. Methods in Molecular Biology, vol 2098. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-0207-2_3
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DOI: https://doi.org/10.1007/978-1-0716-0207-2_3
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