Abstract 4573: Immune infiltrate profiling for progressive malignant stages of cutaneous squamous cell carcinoma

Abstract

Abstract Cutaneous squamous cell carcinoma (cSCC) is the most common human cancer, affecting more than 300,000 individuals in the United States annually. Although, most cSCC can be treated successfully by surgery and/or radiation, a significant percentage of cSCC are aggressive and often unresectable and/or can metastasize to the lymph nodes. Organ transplant patients are at a significantly higher risk for cSCC due to a compromised immune system. Recently, the PD-1 inhibitor cemiplimab was approved for the treatment of patients with metastatic cSCC or patients with locally advanced cSCC who are not candidates for curative surgery or curative radiation. This suggests a critical role of immune cells in modulation of disease progression in cSCC. Hence, immune profiling of cSCC is important in identifying novel agents that could benefit patients. Our objective was to employ immunohistochemistry (IHC) to characterize the immune cell infiltrate in normal skin and compare it to actinic keratosis (AK), cSCC and metastatic cSCC (cSCC-M), in order to investigate the immune phenotype associated with progressive stages of malignancy. Our results suggest that AK, cSCC and cSCC-M exhibit significantly higher levels of CD3+, CD4+ and CD8+ T-cells compared to normal skin. Although, the number of CD3+ T-cells are comparable in AK, cSCC and cSCC-M, the CD8+ T-cells show higher infiltration in cSCC-M compared with cSCC and AK. The FOXP3+ Regulatory T-cells (T-reg) display higher abundance with progressive stages of carcinogenesis. However, surprisingly no significant alterations were observed in the abundance of CD4+ T-cells among AK, cSCC and cSCC-M. We also found that the CD68+ Tumor-associated macrophages (TAMs) exhibit a trend of increasing abundance with progressive disease stage. Our study suggests that the CD8+ T-cell population in cSCC-M could be potentially exhausted in the immune hostile tumor micro-environment (TME) constituted by T-reg and TAMs. Alternatively, CD8+ T-cells themselves might express FOXP3 and other immune suppressive factors, thereby reaching a state of anergy. Immunotherapy continues to be a burgeoning field and holds exciting therapeutic prospects in the treatment of cSCC. Moreover, transplant patients with aggressive cSCC are a unique patient population that could benefit from immunotherapy. Citation Format: Md Maksudul Alam, Alok Khandelwal, Tara Moore-Medlin, Hillary Savage, Xiaohui Ma, Cherie-Ann Nathan. Immune infiltrate profiling for progressive malignant stages of cutaneous squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4573.