Tumor-infiltrating lymphocytes in necrotic tumors after melanoma neoadjuvant anti-PD1 therapy correlate with pathological response and recurrence-free survival.
Kevin L Ma, Tara C Mitchell, Meaghan Dougher, Cimarron E Sharon, Gabriella N Tortorello, David E Elder, Eric E Morgan, Phyllis A Gimotty, Alexander C Huang, Ravi K Amaravadi, Lynn M Schuchter, Ahron Flowers, John T Miura, Giorgos C Karakousis, Xiaowei Xu
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引用次数: 0
Abstract
Purpose: Neoadjuvant anti-PD1 therapy in melanoma may increase tumor-infiltrating lymphocytes (TILs), and more TILs are associated with better treatment response. A major pathological response (MPR) in melanoma after neoadjuvant anti-PD1 therapy usually comprises tumor necrosis and fibrosis. The role of TILs in necrotic tumor necrosis (nTILs) has not been explored.
Experimental design: We performed CD3 and CD8 immunohistochemical stains on 41 melanomas with geographic necrosis. 14 were immunotherapy-naïve, and 27 had been treated with one dose of neoadjuvant anti-PD-1 in two clinical trials. CD3+ and CD8+ nTILs were graded as absent/minimal or moderate/brisk. The percentage of necrotic areas in the tumor bed before and after treatment was quantified. Endpoints were MPR and 5-year recurrence-free survival (RFS).
Results: In the immunotherapy-naïve cohort, 3/14 (21%) specimens had moderate/brisk CD3+, and 2/14 (14%) had moderate/brisk CD8+ nTILs. In the treated cohort, 16/27 (59%) specimens had moderate/brisk CD3+, and 15/27 (56%) had moderate/brisk CD8+ nTILs, higher than the naïve cohort (CD3, p=0.046; CD8, p=0.018). Tumor necrosis was significantly increased after anti-PD1 therapy (p=0.007). In the treated cohort, moderate/brisk CD3+ and CD8+ nTILs correlated with MPR (p=0.042, p=0.019, respectively). Treated patients with moderate/brisk CD3+ nTILs had higher 5-year RFS than those with absent/minimal nTILs (69% versus 0%; p=0.006). This persisted on multivariate analysis (HR 0.16, 95% CI 0.03-0.84, p=0.03), adjusted for pathologic response, which was borderline significant (HR 0.26, 95% CI 0.07-1.01, p=0.051).
Conclusions: CD3+ and CD8+ nTILs are associated with pathological response and 5-year RFS in melanoma patients after neoadjuvant anti-PD1 therapy.
期刊介绍：
Clinical Cancer Research is a journal focusing on groundbreaking research in cancer, specifically in the areas where the laboratory and the clinic intersect. Our primary interest lies in clinical trials that investigate novel treatments, accompanied by research on pharmacology, molecular alterations, and biomarkers that can predict response or resistance to these treatments. Furthermore, we prioritize laboratory and animal studies that explore new drugs and targeted agents with the potential to advance to clinical trials. We also encourage research on targetable mechanisms of cancer development, progression, and metastasis.
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