Although human cancers express antigens recognized by the immune system, immune responses don't always control tumor growth; tumor cells may adapt to avoid immune surveillance.

Although melanoma is one of the few spontaneously regressing solid tumors, tumor-specific T cells are often suppressed through inhibitory signals between lymphocyte and melanoma cell. The co-inhibitory molecule B7-H1 is often overexpressed on tumor cells. It impairs T-cell responses through binding of its co-inhibitory receptor PD-1, which is highly expressed on tumor-infiltrating lymphocytes. Investigators examined B7-H1 expression in melanocytic tumors to investigate a link between native, tumor-infiltrating lymphocytes (TILs) and B7-H1 levels.


Of 150 lesions, 57 (38%) were B7-H1+. Only a single case of metastatic melanoma showed broad B7-H1 expression unassociated with TILs, and 3 cases (1 primary; 2 metastases) showed mixed patterns. Evaluation of TILs showed that 98% of B7-H1+ tumors were associated with TILs versus only 28% of B7-H1- tumors. The B7-H1+ melanocytes were most often found adjacent to the TILs.

B7-H1 expression levels did not differ between nevi and melanoma, suggesting that the immunostimulatory pathway operates independently of tumorigenic signals. Superficial spreading and nodular melanomas were B7-H1+ significantly more often than were lentigo maligna, acral lentiginous, or desmoplastic melanomas. In primary melanomas, B7-H1 expression did not correlate with overall survival but in metastatic melanoma, B7-H1 expression by tumor cells was significantly correlated with improved survival. Interferon-{gamma}, a primary inducer of B7-H1 expression, was detected at the interface of B7-H1+ tumors and TILs, suggesting that TILs may actually mediate their own inhibition by secreting cytokines that drive tumor B7-H1 expression.


Citation(s):

Taube JM et al. Colocalization of inflammatory response with B7-H1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Sci Transl Med 2012 Mar 28; 4:127ra37.