PD-1 blockade reverses viral infection-induced loss of anti-tumor CD8+ T cell responses

Background Emerging epidemiologic studies describe an increased prevalence of tumors in patients with non-oncogenic chronic viral disease (e.g., non-AIDS-defining cancers in HIV and non-hepatic cancers in HCV). However, there is a lack of basic understanding by what mechanism infections result in increased unrelated cancer formation (i.e., of cancers in tissues not associated with the infection), and what role immunotherapy may have in the rescue of immune responses under this condition. We hypothesized that viral infections establish an immunological environment that leads to the preferential loss of anti-tumor (i.e., anti-self antigen) CD8+ T cells, resulting in the inability of the host to avert tumor growth, and further that immunotherapy can reverse this detrimental loss. Methods