Melanoma in people living with HIV: antigen-presentation loss, spatial immune escape, and inclusive immunotherapy trials.

Background: People living with HIV (PLWH) experience a growing burden of non-AIDS-defining malignancies in the era of effective antiretroviral therapy. Melanoma is an informative but understudied example because its progression and response to immune checkpoint inhibitors are shaped by host immunity and tumor antigen presentation. Yet PLWH have often been excluded from, or only conditionally included in, immunotherapy trials, leaving limited evidence to guide care. Scope: Emerging clinical and translational studies suggest that melanoma in PLWH may differ from melanoma in HIV-negative patients not only in outcomes and treatment access, but also in antitumor immune organization. This Perspective proposes a spatial immuno-oncology framework in which chronic immune perturbation, impaired antigen presentation, exhausted T-cell states, and suppressive myeloid programs may converge in candidate tumor regions that are less visible to adaptive immunity. Implications: We highlight the need for batch-balanced spatial profiling cohorts, validation of antigen-presentation pathways at the protein level, prospective immunotherapy studies on tissue samples, and trial eligibility criteria that safely include PLWH.