Induction of oligoclonal CD8 T cell responses against pulmonary metastatic cancer by a phospholipid-conjugated TLR7 agonist

Abstract

Significance A major goal of cancer immunotherapy is the expansion and/or reactivation of cytotoxic CD8 + T cell responses against malignant cells. We previously showed that the direct injection of toll-like receptor 7 (TLR7) agonists into primary tumors can induce tumor-specific oligoclonal T cell responses whose magnitude correlates with therapeutic efficacy. However, tumors are not always accessible to local therapy. Here, we demonstrate in murine lung metastasis models that single systemic administration of a phospholipid conjugated TLR7 agonist can also expand tumor-specific cytotoxic T cells that are shared by different animals. The expansion can be achieved without causing apparent toxicity. Similar technology combining immune repertoire analysis and immunomodulatory drugs can help to guide the development of optimal immunotherapeutic regimens in cancer patients.