Abstract SY21-03: Organ-specific responses to targeted and immunotherapies

Abstract

Abstract The response to treatment of widely disseminated disease can vary depending on the site of metastasis. In some cases, lesions at one site respond to treatment, while disease at other sites continues to grow. This is seen in the context of melanoma treatment with targeted therapy, with some patients having good responses in the liver, while disease in the brain and bone continues apace. This can be attributed to differences in the microenvironment of lesions in different organs, although other factors undoubtedly contribute. It is also increasingly clear that there is an interplay between the site of metastasis and responses to immunotherapy. Liver metastases are particularly difficult to treat compared to other metastatic locations. Moreover, the presence of liver metastases reduces the efficacy of immunotherapy to control disease at other sites in the same patient. Thus, liver metastases confer systemic tolerance. This is likely linked to the liver being a ‘tolerogenic’ organ with a role in modulating the body’s response to commensal bacteria in the gut. To investigate this, we have established an experimental melanoma model of systemic immune tolerance being conferred by liver metastases. We will present results on the mechanism by which liver metastases hinder not only their response to immunotherapy, but also the response of other distant lesions. Citation Format: Erik Sahai. Organ-specific responses to targeted and immunotherapies. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr SY21-03.