PD-1 inhibitors are known to be effective in melanoma; however, a considerable proportion
of patients fail to respond to therapy, necessitating the identification of predictive
markers. We examined the predictive value of tumor cell HLA class I and II expression
and immune cell infiltration in melanoma patients treated with PD-1 inhibitors. Pretreatment
surgical samples from 40 stage IV melanoma patients were studied immunohistochemically
for melanoma cell expression of HLA class I molecules (using four antibody clones
with different specificities), HLA-II, and immune cell infiltration (using a panel
of 10 markers). Among the responders, the ratio of patients showing melanoma cell
HLA-II expression was higher compared to non-responders (p = 0.0158), and similar
results were obtained in the case of two anti-HLA-I antibodies. A combined score of
HLA-I/II expression also predicted treatment response (p = 0.0019). Intratumoral infiltration
was stronger in the responders for most immune cell types. Progression-free survival
showed an association with HLA-II expression, the combined HLA score, and the density
of immune cells expressing CD134 and PD-1, while overall survival was significantly
associated only with HLA class II expression. Our findings corroborate previous results
indicating the importance of immune cell infiltration and tumor cell HLA-II expression
in the efficacy of PD-1 inhibitor treatment in a “real world” patient cohort and suggest
the potential predictive role of HLA class I expression.
