Malignant cell expression of the aryl hydrocarbon receptor induces PD-L1 and immunosuppression in models of oral and lung cancer

• DOI: 10.4049/jimmunol.208.supp.178.11
• Publication Date: 2023-01-02T16:54:01Z
• Authors: Megan Snyder; Jessica Kenison; Brian Lara; Zhongyan Wang; Tachira Pichardo; Kangkang Yang; Sarah Mazzilli; David Sherr
• Keywords: Immunosuppression

Abstract Immunotherapy has shown dramatic results in treating cancer but only a minority of patients, so there is unmet need to understand the regulation immune suppression tumors. We have that aryl hydrocarbon receptor (AhR) central player regulating checkpoints oral squamous cell carcinoma (OSCC) and may play similar role lung cancer. Orthotopic transplant mouse AhR-knockout (KO) OSCC (MOC1) cells led complete rejection tumor formation coupled with increased T activation draining lymph nodes (tdLNs) signaling tongues, whereas wild type (WT) challenge upregulation exhaustion pathways checkpoint molecules. Similar patterns AhR-facilitated protection appear our model. On average, mice transplanted subcutaneously CMT167AhRKO adenocarcinoma survive up twice as long their WT-challenged counterparts; 50% CMT167AhRKO-transplanted never grow also were partially protected from CMT167WT cells. CMT167WT-transplanted exhibited numbers CD4+ CD8+ tdLNs decreased trafficking tumors while proportion PD1+, CTLA4+ Lag3+ significantly lower AhRKO both lines decreases PD-L1 expression by 50%, suggesting mechanism escape WT Thus, immunological following transplantation CMT167 MOC1 suggests downregulation on malignant at least responsible for enhancement supports AhR’s potential viable immunotherapeutic target two cancers. Supported grants NIH (R21 ES029624-01, R01 ES029136) well Find Cause Breast Cancer Foundation Johnson & Lung Initiative.