An established tumor is a complex tissue composed of tumor cells, stromal cells, inflammatory cells, vasculatures, and extracellular matrices, all of which are defined together as the tumor microenvironment. Successful tumor control by immunotherapy requires activation of the immune system, expansion of the effector cells, infiltration of activated effector cells to the tumor tissue, and destruction of the tumor cells. Our previous studies have showed that anti-tumor effect of current tumor immunotherapies, such as checkpoint blockade, relies on a significant number of spontaneous tumor infiltrating lymphocytes. However, established tumors often inhibit peripheral lymphocytes entering tumor tissues for tumor destruction. Inflammatory mediators, especially cytokines, chemokines, and adhesion molecules, play important roles in the recruitment and activation of various types of innate and adaptive immune cells. As a proof-of-concept study, we targeted tumor tissues with LIGHT, a member of the tumor necrosis factor super family. Our data suggested that targeting tumor with LIGHT is able to induce the production of several cytokines/chemokines, which recruit T cells into tumor microenvironment, leading to tumor regression. Furthermore, combination therapy with LIGHT is able to overcome tumor resistance to checkpoint blockade. Thus, these data suggested that manipulating tumor microenvironment with cytokines/chemokines that are able to recruit effector cells represents a promising strategy for tumor immunotherapy. To better understand the role of individual cytokine/chemokine, we utilized chemokine array to systemically analyze tumor microenvironments. By comparing chemokine profiles from immunotherapy-sensitive and -insensitive tumors, we found a significant difference which might be responsible for their sensitivity to immunotherapies. Sensitive tumor is characterized with a higher level of chemokines associated with lymphoid cell trafficking, such as CXCL9 and CCL22. In contrast, insensitive tumor is characterized by a higher levels of chemokines associated with myeloid cell, such as MCP-1 and CCL11. The contributions and their therapeutic potentials of these cytokines/chemokines will be studied in the next step.
Citation Format: Haidong Tang, Xiangyan Qiu, Yang Wang, Yang-Xin Fu. Manipulating tumor microenvironment for immunotherapy [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr A112.
- ©2016 American Association for Cancer Research.