The Tumor Microenvironment of Cutaneous Squamous Cell Carcinoma in Immunosuppressed Patients

Nonmelanoma skin cancer is the most common malignancy and immunosuppression is a key risk factor. Despite the promising data demonstrating the efficacy of immune checkpoint inhibition in the treatment of cutaneous squamous cell carcinoma (cSCC), most immunosuppressed patients are not included in immunotherapy trials due to the risk for toxicity and the lack of data regarding cSCC immune landscape in immunosuppressed patients. To characterize the specific alterations accounting for a diminished antitumor immune response in immunosuppressed patients, we used multispectral imaging on cSCC pathology specimens from immunosuppressed patients with age and stage matched immunocompetent controls. We show that densities of CD68+ cells are diminished in immunosuppressed patients. Moreover, using an organ transplant recipient cohort from two cancer centers, we found significantly lower effector T-cells densities as compared with controls. Overall, density of CD68+ and CD8+LAG3+ cells were predictors of disease-specific and disease-free survival. These findings provide insight into the patterns of immune infiltrating cells in patients with different types of immunosuppression; leading us to conjecture that different immune based therapeutic approaches may be needed to treat immunosuppressed cSCC patients.