Immunotherapy with checkpoint inhibitors has proven to be highly effective, with durable responses in a subset of patients. In an effort to broaden the number of responding individuals, overcome resistance to single-agent therapy and extend the duration of responses, combination of immunotherapy with other treatments such as chemotherapy is currently being tested in multiple clinical trials. Importantly, combination of immunotherapy with standard of care chemotherapy could bring the benefits of immunotherapy into earlier lines of treatment.
Here, we have evaluated the effects of different classes of chemotherapeutic agents alone or in combination with anti-PD-L1 treatment in syngeneic murine tumor models. We have found that combination of anti-PD-L1 with various alkylating agents, taxanes and platins caused differential changes on the frequency and number of intratumoral immune cell subsets, but did not antagonize the functional changes mediated by anti-PD-L1 treatment. Importantly, by comparing the effects of these chemotherapies in different tumor models, we have observed that their effects are model-specific. These differences may be due to tumor-specific immune composition and tumor intrinsic responses to different chemotherapies.
Our results demonstrate that in the models we have tested, chemotherapeutic agents do not appear to directly antagonize the activity of anti-PD-L1 as measured by pharmacodynamic changes in immune cell activation although some differences can be observed in the frequency and number of certain intratumoral immune cell subsets. Additionally, our findings also reveal that tumor models might respond differently to the same chemotherapeutic treatment adding complexity to how we evaluate the effect of combination treatments with chemotherapy. Nonetheless, our results suggest a rationale for combining immunotherapy with chemotherapy in the clinic, although consideration should be taken when generalizing results from mouse tumor models.
Citation Format: Rafael Cubas, Marina Moskalenko, Jeanne Cheung, Shiuh-Ming Luoh, Erin McNamara, Marcia Belvin, Jeong Kim, Stephen Gould. Effect of different standard of care chemotherapeutics on anti-PD-L1 responses in syngeneic mouse tumor models [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 A114.