CD39、CD103、CD137 和 PD-1 作为自然发生的肿瘤抗原特异性 TILs 生物标志物的系统分析

The detection of tumor-specific T cells in solid tumors is integral to interrogate endogenous antitumor responses and to advance downstream therapeutic applications. Multiple biomarkers are reported to identify endogenous tumor-specific tumor-infiltrating lymphocytes (TILs), namely CD137, PD-1, CD103, and CD39; however, a direct comparison of these molecules has yet to be performed.

We evaluated these biomarkers in primary human ovarian tumor samples using single-cell mass cytometry to compare their relative phenotypic profiles, and examined their response to autologous tumor cells ex vivo. PD-1 + , CD103 + , and CD39 + TILs all contain a CD137 + cell subset, while CD137 + TILs highly co-express the aforementioned markers. CD137 + TILs exhibit the highest expression of cytotoxic effector molecules compared to PD-1 + , CD103 + , or CD39 + TILs.

Removal of CD137 + cells from PD-1 + , CD103 + , or CD39 + TILs diminish their IFN-γ secretion in response to autologous tumor cell stimulation, while CD137 + TILs maintain high HLA-dependent IFN-γ secretion. CD137 + TILs exhibited an exhausted phenotype but with CD28 co-expression, suggesting possible receptiveness to reinvigoration via immune checkpoint blockade.

Together, our findings demonstrate that the antitumor abilities of PD-1 + , CD103 + , and CD39 + TILs are mainly derived from a subset of CD137-expressing TILs, implicating CD137 as a more selective biomarker for naturally occurring tumor-specific TILs.