Adoptively transferred tumor-infiltrating T cells target somatic cancer mutations in a human papillomavirus+ cancer patient with complete tumor regression

Background Adoptive transfer of tumor-infiltrating lymphocytes (TIL) can mediate complete regression of metastatic cervical cancer, but the immunological landscape of the anti-tumor T cell responses in these patients is not fully understood. Reactivity against the human papillomavirus (HPV)-derived antigens may contribute to the clinical responses, but whether other immunogenic tumor antigens are also targeted by these effective TIL is unknown. Tumor-specific neo-antigens arising from somatically mutated genes are thought to be important for the therapeutic efficacy of immunotherapies in a variety of solid tumors. Cervical cancers also harbor somatic mutations that may be the targets of tumor-specific T cells. Here we assessed whether mutated neo-antigens were the targets of clinically effective TIL in a patient with metastatic HPV16+ cervical cancer who experienced complete tumor regression, ongoing beyond 2 years, after TIL therapy.