High fractions of TCF7+ T-cells in tertiary lymphoid structures are associated with improved survival in patients with metastatic melanoma

Summary: Abstract Body: Tertiary lymphoid structures (TLS) are ectopic immune cell aggregates that develop in non-lymphoid sites during chronic inflammation. TLS have been shown to be associated with enhanced survival outcomes in metastatic melanoma, yet the underlying mechanism of TLS remains poorly understood. Transcription factor 7 (TCF7) is a marker of stem cell-like T-cells with the ability to proliferate and self-renew and is also associated with improved survival in melanoma. Increased TCF7 expression is theorized to improve immune checkpoint blockade by inducing a robust T-cell response. Thus, this study aimed to investigate varying levels of intra-TLS TCF7+ T-cells and their prognostic potential in metastatic melanoma. Cutaneous metastatic melanomas were evaluated for TLS presence and TCF7 expression by multiplex immunofluorescent histology. CD3+CD8- (CD4+) and CD3+CD8+ (CD8+) T-cells were enumerated from 15 TLS specimens with Halo software (Indica Labs) and densities of T-cells expressing TCF7 was calculated. The densities of TCF7+ T-cells were then dichotomized into high (TCF7high) and low (TCF7low) groups using the Contal-O’ Quigley method. Associations with survival were assessed using log-rank tests. We found that in patients with metastatic melanoma, patients with CD4+TCF7high (Median OS 50.9 vs 11.9 months, p = 0.005) and CD8+TCF7high (Median OS 120.5 vs 20.6 months, p = 0.02) had significantly prolonged survival compared to patients with CD4+TCF7low and CD8+TCF7low, respectively. These findings suggest TCF7+ T-cells are an important element of TLS that contributes to its survival benefits in metastatic melanoma. TCF7+ T-cells show promise as a valuable prognostic marker and a novel therapeutic target for immunotherapies in the treatment of melanoma and potentially other cancers. Leon Zheng¹, Richard Chung¹, Priya Katyal², Nicole Edmonds³, Sarah Gradecki⁴, Ileana Mauldin⁵ 1. University of Virginia School of Medicine, Charlottesville, VA, United States. 2. Georgetown University School of Medicine, Washington, DC, United States. 3. Dermatology, University of Virginia, Charlottesville, VA, United States. 4. Pathology, University of Virginia, Charlottesville, VA, United States. 5. Surgery, University of Virginia, Charlottesville, VA, United States. Pigmentation, Melanoma, and Melanoma Immune Surveillance