TY - JOUR
T1 - Progressive upregulation of PD-1 in primary and metastatic melanomas associated with blunted TCR signaling in infiltrating T lymphocytes
AU - Chapon, Maxime
AU - Randriamampita, Clotilde
AU - Maubec, Eve
AU - Badoual, Cécile
AU - Fouquet, Stéphane
AU - Wang, Shu Fang
AU - Marinho, Eduardo
AU - Farhi, David
AU - Garcette, Marylène
AU - Jacobelli, Simon
AU - Rouquette, Alexandre
AU - Carlotti, Agnès
AU - Girod, Angélique
AU - Prévost-Blondel, Armelle
AU - Trautmann, Alain
AU - Avril, Marie Françoise
AU - Bercovici, Nadège
PY - 2011/1/1
Y1 - 2011/1/1
N2 - Programmed death-1 (PD-1) is involved in T-cell tolerance to self-antigens. For some cancers, it has been suggested that the expression of a ligand of PD-1, namely PD-L1, could contribute to tumor escape from immune destruction. Nevertheless, the relationship between PD-1 expression on tumor-infiltrating T lymphocytes (TILs), disease stage, and TIL responsiveness is still poorly documented. In this study, we show that freshly isolated CD4+ and CD8+ TILs express substantial levels of PD-1 in primary melanomas. The expression of PD-1 was further increased at later stages in distant cutaneous metastases, especially on CD8+ TILs. The expression of PD-1 ligands was frequent only in metastases, on both tumor cells and tumor-derived myeloid cells. TILs isolated from these cutaneous tumors are poorly reactive ex vivo, with blunted calcium response and IFN-γ production after TCR stimulation. Surprisingly, in distinct parts of a primary melanoma, either invasive or regressing, we show that TILs similarly express PD-1 and remain dysfunctional. The expressions of PD-1 and PD-L1 in metastatic melanoma lesions could be considered as witnesses of an unsuccessful anti-tumoral immune response, but the direct involvement of PD-1 in the severity of the disease, and the importance of TILs in tumor regression, remain to be established.
AB - Programmed death-1 (PD-1) is involved in T-cell tolerance to self-antigens. For some cancers, it has been suggested that the expression of a ligand of PD-1, namely PD-L1, could contribute to tumor escape from immune destruction. Nevertheless, the relationship between PD-1 expression on tumor-infiltrating T lymphocytes (TILs), disease stage, and TIL responsiveness is still poorly documented. In this study, we show that freshly isolated CD4+ and CD8+ TILs express substantial levels of PD-1 in primary melanomas. The expression of PD-1 was further increased at later stages in distant cutaneous metastases, especially on CD8+ TILs. The expression of PD-1 ligands was frequent only in metastases, on both tumor cells and tumor-derived myeloid cells. TILs isolated from these cutaneous tumors are poorly reactive ex vivo, with blunted calcium response and IFN-γ production after TCR stimulation. Surprisingly, in distinct parts of a primary melanoma, either invasive or regressing, we show that TILs similarly express PD-1 and remain dysfunctional. The expressions of PD-1 and PD-L1 in metastatic melanoma lesions could be considered as witnesses of an unsuccessful anti-tumoral immune response, but the direct involvement of PD-1 in the severity of the disease, and the importance of TILs in tumor regression, remain to be established.
UR - http://www.scopus.com/inward/record.url?scp=79956048616&partnerID=8YFLogxK
U2 - 10.1038/jid.2011.30
DO - 10.1038/jid.2011.30
M3 - Article
AN - SCOPUS:79956048616
SN - 0022-202X
VL - 131
SP - 1300
EP - 1307
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 6
ER -