Landscape of immunogenic tumor antigens in successful immunotherapy of virally induced epithelial cancer

TLDR

Adoptive cell transfer targeting nonviral antigens can cure HPV‑driven epithelial tumors, yet the reasons for variable patient responses remain unclear. The study examined antitumor T‑cell responses in HPV‑positive cervical cancers that achieved complete regression. Reactive T cells targeted cancer germline antigens or novel neoantigens rather than viral antigens, challenging the prevailing view that viral antigen responses drive therapeutic efficacy in HPV‑driven cancers. Stevanović et al., Science, this issue, p.

Abstract

Targeting nonviral antigens in viral-driven cancer Adoptive cell transfer harnesses a patient's own T cells to destroy cancer. The strategy can successfully treat epithelial tumors driven by human papillomavirus (HPV), but it remains unclear why only some patients respond. Stevanović et al. examined the antitumor T cell response associated with HPV + cervical cancers that underwent complete regression. Unexpectedly, reactive T cells were not directed against virally associated antigens, but rather against cancer germline antigens or neoantigens not previously recognized by the immune system. These findings counter the widely held belief that T cell responses against viral antigens are responsible for therapeutic effects in HPV-driven cancers. Science , this issue p. 200