Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.
Columbia University Vagelos College of Physicians and Surgeons, New York, New York.
Clin Cancer Res. 2024 Nov 1;30(21):4987-4994. doi: 10.1158/1078-0432.CCR-23-3775.
Neoadjuvant anti-PD-1 therapy in melanoma may increase tumor-infiltrating lymphocytes (TIL), and more TIL are associated with better treatment response. A major pathologic response (MPR) in melanoma after neoadjuvant anti-PD-1 therapy usually comprises tumor necrosis and fibrosis. The role of TIL in necrotic tumor necrosis (nTIL) has not been explored.
We performed CD3 and CD8 IHC stains on 41 melanomas with geographic necrosis. Of the 41, 14 were immunotherapy-naïve, and 27 had been treated with one dose of neoadjuvant anti-PD-1 in two clinical trials. CD3+ and CD8+ nTIL were graded as absent/minimal or moderate/brisk. The percentage of necrotic areas in the tumor bed before and after treatment was quantified. The endpoints were MPR and 5-year recurrence-free survival (RFS).
In the immunotherapy-naïve cohort, 3/14 (21%) specimens had moderate/brisk CD3+, and 2/14 (14%) had moderate/brisk CD8+ nTIL. In the treated cohort, 16/27 (59%) specimens had moderate/brisk CD3+, and 15/27 (56%) had moderate/brisk CD8+ nTIL, higher than those of the naïve cohort (CD3, P = 0.046; CD8, P = 0.018). Tumor necrosis was significantly increased after anti-PD-1 therapy (P = 0.007). In the treated cohort, moderate/brisk CD3+ and CD8+ nTIL correlated with MPR (P = 0.042; P = 0.019, respectively). Treated patients with moderate/brisk CD3+ nTIL had higher 5-year RFS than those with absent/minimal nTIL (69% vs. 0%; P = 0.006). This persisted on multivariate analysis (HR, 0.16; 95% confidence interval, 0.03-0.84; P = 0.03), adjusted for pathologic response, which was borderline significant (HR, 0.26; 95% confidence interval, 0.07-1.01; P = 0.051).
CD3+ and CD8+ nTIL are associated with pathologic response and 5-year RFS in patients with melanoma after neoadjuvant anti-PD-1 therapy.
黑色素瘤的新辅助抗 PD-1 治疗可能会增加肿瘤浸润淋巴细胞（TIL），更多的 TIL 与更好的治疗反应相关。新辅助抗 PD-1 治疗后黑色素瘤的主要病理缓解（MPR）通常包括肿瘤坏死和纤维化。TIL 在坏死性肿瘤坏死（nTIL）中的作用尚未得到探索。
我们对 41 例具有地理性坏死的黑色素瘤进行了 CD3 和 CD8 的免疫组化染色。在这 41 例中，14 例为免疫治疗初治患者，27 例在两项临床试验中接受了一次新辅助抗 PD-1 治疗。CD3+和 CD8+ nTIL 分为无/少量或中/大量。治疗前后肿瘤床内坏死区域的百分比进行了量化。终点是 MPR 和 5 年无复发生存率（RFS）。
在免疫治疗初治组中，14 例中有 3 例（21%）标本的 CD3+为中/大量，14 例中有 2 例（14%）标本的 CD8+为中/大量。在治疗组中，27 例中有 16 例（59%）标本的 CD3+为中/大量，27 例中有 15 例（56%）标本的 CD8+为中/大量，高于初治组（CD3，P=0.046；CD8，P=0.018）。抗 PD-1 治疗后肿瘤坏死明显增加（P=0.007）。在治疗组中，中/大量 CD3+和 CD8+ nTIL 与 MPR 相关（P=0.042；P=0.019）。中/大量 CD3+ nTIL 的治疗患者 5 年 RFS 高于无/少量 nTIL 的患者（69% vs. 0%；P=0.006）。在多变量分析中，这种情况仍然存在（HR，0.16；95%置信区间，0.03-0.84；P=0.03），经病理反应调整后，这一结果接近显著（HR，0.26；95%置信区间，0.07-1.01；P=0.051）。
新辅助抗 PD-1 治疗后黑色素瘤患者的 CD3+和 CD8+ nTIL 与病理反应和 5 年 RFS 相关。
