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The highly immunogenic human tumor antigen NY-ESO-1 (ESO) is a target of choice for anti-cancer immune therapy. In this study, we assessed spontaneous antibody (Ab) responses to ESO in a large cohort of patients with primary breast cancer (BC) and addressed the correlation between the presence of anti-ESO Ab, the expression of ESO in the tumors and their characteristics. We found detectable Ab responses to ESO in 1% of the patients. Tumors from patients with circulating Ab to ESO exhibited common characteristics, being mainly hormone receptor (HR)- invasive ductal carcinomas of high grade, including both HER2- and HER2+ tumors. In line with these results, we detected ESO expression in 20% of primary HR- BC, including both ESO Ab+ and Ab- patients, but not in HR+ BC. Interestingly, whereas expression levels in ESO+ BC were not significantly different between ESO Ab+ and Ab- patients, the former had, in average, significantly higher numbers of tumor-infiltrated lymph nodes, indicating that lymph node invasion may be required for the development of spontaneous anti-tumor immune responses. Thus, the presence of ESO Ab identifies a tumor subtype of HR- (HER2- or HER2+) primary BC with frequent ESO expression and, together with the assessment of antigen expression in the tumor, may be instrumental for the selection of patients for whom ESO-based immunotherapy may complement standard therapy. [ABSTRACT FROM AUTHOR]

The role of TH17 cells in cancer is being investigated, but the existence of tumor antigen-specific TH17 cells has yet to be ascertained. Here, we report the first description of a spontaneous TH17 (IL-17+) response to the important tumor antigen MAGE-A3, which occurred concurrently with a TH1 (IFN-γ+) response in a lung cancer patient. MAGE-A3-specific interleukin (IL)-17+) T cells were mainly CCR7+) central memory T cells, whereas IFN-γ+) cells were enriched for CCR7-) effector memory T cells. An assessment of the fine specificity of antigen recognition by these T cells indicated that the CCR6+) CCR4+) and CCR6+)CXCR3+) fractions contained the same TH17/TH1 population at early and late differentiation stages, respectively, whereas the CCR6-) CXCR3+) fraction contained a distinct TH1 population. These findings are important because they suggest a differentiation model in which tumor antigen-specific CD4+) T cells that are primed under TH17 polarizing conditions will progressively convert into IFN-γ-secreting cells in vivo as they differentiate into effector T cells that can effectively attack tumors. [ABSTRACT FROM AUTHOR]