Ex-vivo analysis of CD8+ T cells infiltrating colorectal tumors identifies a major effector-memory subset with low perforin content.
Previous studies have indicated that the infiltration of CD8+ T cells in colorectal cancer is an independent predictor of increased survival but clinical observations have suggested that the cytotoxic function of CD8+ T cells infiltrating colorectal cancer may often be limited. In this study, we have assessed the phenotype of colorectal cancer CD8+ tumor-infiltrating lymphocytes (TILs) isolated ex vivo from tumor tissue, and assessed the perforin content of TIL with respect to their location using immunohistochemistry. We found that CD8+ T cells TILs isolated from colorectal cancer are mainly composed of antigen-experienced cells of effector memory type (TEM, CD45RA-CCR7-, and CD27+/CD28- or CD27-/CD28-), and contain only minor proportions of terminally differentiated CD8+ T cells (TEMRA, CD45RA+CCR7-). The perforin content of these TILs, however, is significantly lower than that of antigen-experienced T cells in PBMCs due to the much lower levels of perforin found in the CD27-CD28- subset in TILs compared with CD8+ T cells of similar phenotype in PBMCs.
Ye
Sheng-Wei
SW
Department of Colorectal Surgery, Peking University School of Oncology, Beijing Cancer Hospital, No. 52 Fu-cheng Road, Hai-dian District, Beijing 100036, PR China.
Wang
Yu
Y
Valmori
Danila
D
Ayyoub
Maha
M
Han
Yan
Y
Xu
Xiao-Lan
XL
Zhao
Ai-Lian
AL
Qu
Li
L
Gnjatic
Sacha
S
Ritter
Gerd
G
Old
Lloyd J
LJ
Gu
Jin
J
D000230:Adenocarcinoma / Q000276:immunology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D015179:Colorectal Neoplasms / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007156:Immunologic Memory; D016246:Lymphocytes, Tumor-Infiltrating / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D054353:Perforin; D010641:Phenotype; D052899:Pore Forming Cytotoxic Proteins / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin