Circulating tumor antigen-specific regulatory T cells in patients with metastatic melanoma.
Although it is accepted that regulatory T cells (T regs) contribute to cancer progression, most studies in the field consider nonantigen-specific suppression. Here, we show the presence of tumor antigen-specific CD4(+) T regs in the blood of patients with metastatic melanoma. These CD4(+) T regs recognize a broad range of tumor antigens, including gp100 and TRP1 (melanoma tissue differentiation antigens), NY-ESO-1 (cancer/testis antigen) and survivin (inhibitor of apoptosis protein (IAP) family antigen). These tumor antigen-specific T regs proliferate in peripheral blood mononuclear cells (PBMC) cultures in response to specific 15-mer peptides, produce preferentially IL-10 and express high levels of FoxP3. They suppress autologous CD4(+)CD25(-) T cell responses in a cell contact-dependent manner and thus share properties of both naturally occurring regulatory T cells and type 1 regulatory T cells. Such tumor antigen-specific T regs were not detected in healthy individuals. These tumor antigen-specific T regs might thus represent another target for immunotherapy of metastatic melanoma.
Vence
Luis
L
Baylor Institute for Immunology Research and Baylor Research Institute, Baylor University, Dallas, TX 75204, USA.
Palucka
A Karolina
AK
Fay
Joseph W
JW
Ito
Tomoki
T
Liu
Yong-Jun
YJ
Banchereau
Jacques
J
Ueno
Hideki
H
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000097:blood*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D016753:Interleukin-10 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000097:blood* / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D008565:Membrane Proteins / Q000096:biosynthesis; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000378:metabolism; D000077022:Survivin; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*; D014357:Trypsin; D014362:Trypsinogen / Q000096:biosynthesis / Q000378:metabolism; D058951:gp100 Melanoma Antigen
D000951:Antigens, Neoplasm; C107489:BIRC5 protein, human; C104948:CTAG1B protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D051034:Inhibitor of Apoptosis Proteins; D053645:Interleukin-2 Receptor alpha Subunit; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; C548637:PMEL protein, human; D000077022:Survivin; D058951:gp100 Melanoma Antigen; D016753:Interleukin-10; D014362:Trypsinogen; C489303:PRSS1 protein, human; D014357:Trypsin