Abstract S02-02: Covid-19 treatment candidate hydroxychloroquine impairs tumor response to anti-PD1

Abstract

Abstract Background and Aims: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused a worldwide health crisis. As of now, only one treatment has been established for the coronavirus infection disease 2019 (Covid-19), which has disproportionally affected patients with comorbidities such as cancer. Hydroxychloroquine (HCQ) has been studied as a potential treatment for Covid-19. Here we studied whether HCQ treatment could influence the effect of immunotherapy against colorectal and liver cancer. Methods: In vitro studies were conducted to assess the effect of HCQ on lymphocyte activation and proliferation as well as cell growth and antigen presentation. Mouse cell lines used included MC38, CT26, RIL-175, SB1, and LD1 while human tumor cell lines used were TFK-1 and EGI-1. Mice bearing subcutaneous MC38, CT26, and RIL-175 tumors were treated with HCQ, anti-PD1, or both. Tumor volume was measured over 19 days. Systemic and tumor-infiltrating immune cells were analyzed by flow cytometry. Results: HCQ treatment impairs T-cell production of TNF-α and IFNγ in vitro and in vivo. Whereas cell growth was decreased in all tumor cell lines, in vitro treatment of tumor cells with HCQ revealed an upregulation of MHC-1 in CT26, SB1, LD1, TFK-1, and EGI-1 but not in MC38 and RIL-175. HCQ treatment impaired response to anti-PD1 treatment in all subcutaneous models. Compared to control, HCQ treatment led to increased tumor growth in MC38 tumors. Flow cytometry analysis revealed an impaired activation of CD4+ T cells as well as tumor-infiltrating cytotoxic antigen-specific CD8+ T cells. Conclusion: This study shows that HCQ treatment can result in immunotherapy failure due to a systematic immunosuppressive effect that overcomes the increased MHC expression on tumor cells. Citation Format: Simon Wabitsch, Jack C McVey, Chi Ma, Benjamin Ruf, Laurence Diggs, Bernd Heinrich, Tim F Greten. Covid-19 treatment candidate hydroxychloroquine impairs tumor response to anti-PD1 [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr S02-02.