KIF18A expression is increased in cutaneous squamous cell carcinoma regardless of immune status

Summary: Immuno-oncology has revolutionized the treatment of both melanoma and non-melanoma malignancies. In unresectable cutaneous squamous cell carcinoma(CSCC), however, the objective response rate is between 30 and 50%. Moreover, in solid organ transplant recipients(SOTRs) the use of immunotherapy remains a major challenge. Further investigation of anti-tumor agents that are mechanistically distinct from checkpoint inhibitors and can trigger an anti-tumor but not allograft immunity is urgently needed in patients with advanced skin cancers to improve survival. A hallmark of skin cancer is chromosomal instability. KIF18A is an important mediator of mitosis in chromosomally aberrant cancer cells but is not required for cell division in normal diploid cells. KIF18A overexpression has been shown in a variety of solid tumors including breast, colorectal, renal, and liver cancer. To investigate the expression of KIF18A in CSCC, we stained paraffin embedded sections of CSCC from both SOTRs (n=5) and immunocompetent patients (n=6) against KIF18A. Compared to normal adjacent epidermis, tumor tissue has a significantly higher level of KIF18A expression (2.8 vs. 17.3% KIF18A-positive cells, p<0.0001). Expression was also significantly higher in poor vs well-differentiated tumors (27.5 vs 14.8 % KIF18A-positive cells, p= 0.0072), which is consistent with previous data on increased level of somatic copy number aberrations observed in tumors with high-risk histology. The level of expression of KIF18A was not different in CSCCs of SOTRs vs immunocompetent patients, consistent with prior studies which show that when adjusted for T stage, metastatic risk is similar between SOTRs and immunocompetent. Here we demonstrate that KIF18A is highly expressed in CSCC and correlates with aggressive histology. KIF18A inhibitor is currently in clinical trials for advanced malignancies. Its lack of mechanistic dependency on adaptive immunity makes it a promising treatment target for CSSC in SOTRs and patients failing immunotherapy. Madeliene Stump^{1, 2}, Qian Zhan¹, Yuka Hirakawa¹, Rachael A. Clark¹, Chrysalyne Schmults¹ 1. Dermatology, Brigham and Women's Hospital, Boston, MA, United States. 2. Dermatology, Dana-Farber Cancer Institute, Boston, MA, United States. UV Biology/Injury and Non-melanoma Cancers