Abstract 3132: Highly expressed wnt10b is associated with immune repression status in recurrent melanoma patients with positive sentinel lymph nodes

Abstract

Abstract Background: The sentinel lymph node (SLN) is the first immune recognition site during tumor development, making it critically important in the shaping of subsequent adaptive immune responses against tumors. Melanoma patients with a single microscopically positive SLNs are classified as stage III despite the fact that there is significant variation in disease recurrence. Understanding of why there is such a wide disparity in outcomes among these patients may direct us to find a better treatment strategy to reduce recurrence and increase survival. Our previous studies have shown that expression of Wnt10b in the SLN was significantly higher in melanoma patients with recurrence versus those without recurrence. Given the importance of Wnt signaling in the immune response to cancer and the immunosuppression status in local microenvironments in recurrent patients, we suspect that highly expressed Wnt10b may be connected to dysfunction of the immune responses in melanoma patients with recurrence. Hypothesis: Highly expressed Wnt10b represses anti-tumor immune responses and increases the likelihood of recurrence in melanoma patients. Methods: 36 retrospective SLN RNA samples from node-positive melanoma patients were used. 18 were obtained from recurrent melanoma patients and 18 were from melanoma patients without recurrence. We performed RT-PCR to confirm the highly expressed Wnt10b in melanoma patients with recurrence and compared the expression of Wnt pathway receptors FZD3 and LRP5 between the recurrent and non-recurrent melanoma patients. Immunohistochemistry (IHC) was used to check the expression of Wnt10b, CD8; a cell surface marker of cytotoxic T cells; and FoxP3; a transcription factor mostly found in T cells associated with immune suppression; as well as the melanoma cell marker SOX10. CyTOF (Cytometry by Time of Flight) was used to compare the immunophynotype of SLN cells from patients that are projected to have higher chance of recurrence versus those who have lower chance of recurrence. Results: Wnt receptors, FZD3 and LRP5 were overexpressed in recurrent patients versus the patients without recurrence. After the data were adjusted for melanoma tumor burden, the ratio of CD8:FoxP3 was significantly lower in recurrent melanoma patients who had higher Wnt10b expression versus those without recurrence who had lower Wnt10 levels. Patients who are projected to have higher chance of recurrence have lower CD8 Naïve T cells than those who have lower chance of recurrence. Conclusions: Highly expressed Wnt10b in recurrent melanoma patients is associated with immune suppression status in the SLN. Further research is ongoing to define the mechanisms by which Wnt10b suppresses the immune responses in the SLN. These findings may lead to the development of novel therapeutic targets and strategies. Citation Format: Austin McMasters, Hong Li, Hongying Hao, Kelly M. McMasters. Highly expressed wnt10b is associated with immune repression status in recurrent melanoma patients with positive sentinel lymph nodes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3132.