The Characteristics of Naive-like T Cells in Tumor-infiltrating Lymphocytes From Human Lung Cancer.
Adoptive cell therapy using autologous tumor-infiltrating lymphocytes (TILs) or genetically modified lymphocytes from TILs is a new effective approach, but the application of TIL immunotherapy is still limited in many solid tumors. Knowledge of the classification and function of TILs is important to develop personalized immunotherapy with TILs in non-small lung cancer (NSCLC). In this study, we show the characteristics of T-cell subsets in TILs isolated from NSCLC. CD3 CD8 CD45RA T cells outnumbered CD3 CD4 CD45RA T cells in CD45RA TILs, but it was the opposite in CD45RO TILs. Effector memory CD4 T cells predominated in CD4 TILs; about 10% of the stem cell-like memory T cells (Tscm) were detected in TILs. To further analyze their functions, we stimulated TILs from NSCLC patients by mitogens to examine cytokine production. Our data demonstrated that naive-phenotype T cells in TILs secret IFN-γ in abundance; TNF-α-producing T cells were significantly increased in TILs; there were more IL-17-expressing CD4 Tscm cells than other subtypes of CD4T cells in TILs. Our findings indicate that the CD4/CD8 naive-phenotype T cells and Tscm cells in TILs from lung cancer exhibit distinct composition and strong cytokine production. Attributes of Tscm cells from a naive-like T-cell population in TILs are the promising cell type for adoptive cell therapy in human lung cancer.
*Key Laboratory of Tropical Disease Control, Ministry of Education; The Institute of Immunology of Zhong Shan Medical School †The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong ‡College of Life Science of Sun Yat-sen University, Guangzhou, Guangdong, China §Houston Methodist Research Institute, Houston, TX.
Si Yuan
SY
Sheng
Yong
Y
Gu
Chuan Gang
CG
Lu
Ying Ying
YY
Tang
Jian Yong
JY
Zou
Yu Qing
YQ
Zhang
Rong Fu
RF
Wang
Hai
H
Hong
D000328:Adult; D053687:Adult Stem Cells / Q000276:immunology*; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008175:Lung Neoplasms / Q000276:immunology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000637:transplantation; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D020381:Interleukin-17; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens