CD4+ T effectors specific for the tumor antigen NY-ESO-1 are highly enriched at ovarian cancer sites and coexist with, but are distinct from, tumor-associated Treg.

Whereas tumor infiltration by T effectors is generally associated with a more favorable prognosis, the accumulation of CD4(+) regulatory T cells (Treg) within tumors is instead often associated with poor disease outcome. Because approaches to improve antitumor immunity aim, on one hand, at expanding tumor antigen-specific T cells and, on the other, at eliminating or inactivating Treg, an outstanding question is whether, and to what extent, tumor antigen-specific CD4(+) T effectors present at tumor sites overlap with tumor-associated Treg. Here, we used MHC class II/peptide tetramers incorporating an immunodominant peptide from the human tumor-specific antigen NY-ESO-1 to assess antigen-specific CD4(+) T cells among conventional CD4(+) T effectors and Treg at sites of ovarian cancer. We found that, in patients who spontaneously respond to the antigen, the frequency of NY-ESO-1 tetramer(+) cells detected ex vivo was highly enriched in tumors as compared with the periphery. At tumor sites, NY-ESO-1 tetramer(+) cells were detected concomitantly with high proportions of Treg but were distinct from the latter and displayed characteristics of TH1 effectors. Thus, even in the presence of high proportions of Treg, tumor antigen-specific CD4(+) T cells can accumulate in ovarian tumors and maintain an effector phenotype.