Clonal expansion of renal cell carcinoma-infiltrating T lymphocytes

TY - JOUR

T1 - Clonal expansion of renal cell carcinoma-infiltrating T lymphocytes

AU - Sittig, Simone

AU - Køllgaard, Tania

AU - Grønbæk, Kirsten

AU - Idorn, Manja

AU - Hennenlotter, Jörg

AU - Stenzl, Arnulf

AU - Gouttefangeas, Cécile

AU - Thor Straten, Per

PY - 2013

Y1 - 2013

N2 - T lymphocytes can mediate the destruction of cancer cells by virtue of their ability to recognize tumor-derived antigenic peptides that are presented on the cell surface in complex with HLA molecules and expand. Thus, the presence of clonally expanded T cells within neoplastic lesions is an indication of ongoing HLA-restricted T cell-mediated immune responses. Multiple tumors, including renal cell carcinomas (RCC s), are often infiltrated by significant amounts of T cells, the so-called tumor-infiltrating lymphocytes (TILs). In the present study, we analyzed RCC lesions (n = 13) for the presence of expanded T-cell clonotypes using T-cell receptor clonotype mapping. Surprisingly, we found that RCC s comprise relatively low numbers of distinct expanded T-cell clonotypes as compared with melanoma lesions. The numbers of different T-cell clonotypes detected among RCC -infiltrating lymphocytes were in the range of 1-17 (median = 5), and in several patients, the number of clonotypes expanded within tumor lesions resembled that observed among autologous peripheral blood mononuclear cells. Moreover, several of these clonotypes were identical in TILs and PBMCs. Flow cytometry data demonstrated that the general differentiation status of CD8++ TILs differed from that of circulating CD8++ T cells. Furthermore, PD-1 and LAG-3 were expressed by a significantly higher percentage of CD8++ RCC -infiltrating lymphocytes as compared with PBMCs obtained from RCC patients or healthy individuals. Thus, CD8++ TILs display a differentiated phenotype and express activation markers as well as surface molecules associated with the inhibition of T-cell functions. However, TILs are characterized by a low amount of expanded T-cell clonotypes

AB - T lymphocytes can mediate the destruction of cancer cells by virtue of their ability to recognize tumor-derived antigenic peptides that are presented on the cell surface in complex with HLA molecules and expand. Thus, the presence of clonally expanded T cells within neoplastic lesions is an indication of ongoing HLA-restricted T cell-mediated immune responses. Multiple tumors, including renal cell carcinomas (RCC s), are often infiltrated by significant amounts of T cells, the so-called tumor-infiltrating lymphocytes (TILs). In the present study, we analyzed RCC lesions (n = 13) for the presence of expanded T-cell clonotypes using T-cell receptor clonotype mapping. Surprisingly, we found that RCC s comprise relatively low numbers of distinct expanded T-cell clonotypes as compared with melanoma lesions. The numbers of different T-cell clonotypes detected among RCC -infiltrating lymphocytes were in the range of 1-17 (median = 5), and in several patients, the number of clonotypes expanded within tumor lesions resembled that observed among autologous peripheral blood mononuclear cells. Moreover, several of these clonotypes were identical in TILs and PBMCs. Flow cytometry data demonstrated that the general differentiation status of CD8++ TILs differed from that of circulating CD8++ T cells. Furthermore, PD-1 and LAG-3 were expressed by a significantly higher percentage of CD8++ RCC -infiltrating lymphocytes as compared with PBMCs obtained from RCC patients or healthy individuals. Thus, CD8++ TILs display a differentiated phenotype and express activation markers as well as surface molecules associated with the inhibition of T-cell functions. However, TILs are characterized by a low amount of expanded T-cell clonotypes

U2 - 10.4161/onci.26014

DO - 10.4161/onci.26014

M3 - Journal article

C2 - 24228230

SN - 2162-4011

VL - 2

SP - 1

EP - 9

JO - OncoImmunology

JF - OncoImmunology

IS - 9

M1 - e26014

ER -