Abstract 1097: Potentiating antitumor CD4+ T cell responses with chemotherapeutic agents

Abstract

Abstract Chemotherapy is a major treatment modality for many types of cancers. Even though chemotherapeutic drugs are chosen for their cytotoxicity toward cancerous cells, increasing numbers of anticancer drugs have been found to exert immune enhancing effects through a variety of mechanisms. These findings have led to a growing recognition that elicitation of endogenous host immunity may intrinsically contribute to the efficacy of some antineoplastic agents. Although standard chemotherapy can reduce the symptoms of cancer, chemotherapy alone is rarely curative. Tumor relapses often occur in patients after the initial treatment, suggesting that the endogenous antitumor immunity elicited by chemotherapy is not sufficient or durable enough to support long-term therapeutic efficacy. There is accumulating evidence that integration of chemotherapy and immunological maneuvers, such as adoptive T-cell therapy (ACT) and therapeutic vaccines, can effectively treat established tumors. In a mouse model of B-cell lymphoma, we previously reported that polyfunctional CD4+ effector cells arising from ACT play a critical role in sustaining an effective antitumor immunity in the post-chemotherapy setting. In the current study, we have screened a panel of widely used chemotherapeutic agents and identified those that can exert immunostimulatory effects on tumor-specific CD4+ T cells. We also examined the impact of these drugs on lymphoid and myeloid cell homeostasis, and cytokine/chemokine milieu. These data provide insight into the mechanisms by which certain anticancer drugs potentiate antitumor CD4+ T cell responses. Citation Format: Gang Zhou, Xiaoyun Lu. Potentiating antitumor CD4+ T cell responses with chemotherapeutic agents. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1097. doi:10.1158/1538-7445.AM2014-1097