Postoperative tumor recurrence and metastasis remain an extreme challenge in breast cancer. Therapies that target cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) have provided unprecedented clinical benefits in various types of cancer. The aim of this study was to determine whether the combination of anti-CTLA-4 and anti-PD-1 could prevent postoperative breast tumor recurrence and metastasis in breast tumor–bearing mice. The results indicated that the combination of CTLA-4 and PD-1 inhibitors was more effective compared with single inhibitors for mammary tumor growth and prevention of postsurgical tumor recurrence and pulmonary metastasis (P < 0.05), which resulted in prolonged survival (P < 0.05). Analysis of the underlying mechanism revealed that anti-CTLA-4 and anti-PD-1 in combination synergistically promoted the infiltration of CD8+ and CD4+ T cells into tumors (P < 0.05 vs. single inhibitors), thus boosting the antitumor immune responses. In summary, our results revealed that combination immunotherapy with anti-CTLA-4 and anti-PD-1 may present a new, promising regimen to inhibit postoperative breast cancer relapse and lung metastasis and improve patient outcomes, which warrants further investigation in clinical settings.

中文翻译：

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细胞毒性 T 淋巴细胞相关抗原 4 和程序性死亡蛋白 1 抑制剂联合免疫治疗预防术后乳腺肿瘤复发和转移

术后肿瘤复发和转移仍然是乳腺癌的一个极端挑战。针对细胞毒性 T 淋巴细胞相关抗原 4 (CTLA-4) 和程序性细胞死亡蛋白 1 (PD-1) 的疗法在各种类型的癌症中提供了前所未有的临床益处。本研究的目的是确定抗 CTLA-4 和抗 PD-1 的组合是否可以预防乳腺肿瘤小鼠术后乳腺肿瘤的复发和转移。结果表明，CTLA-4 和 PD-1 抑制剂联合使用比单一抑制剂更有效地预防乳腺肿瘤生长和预防术后肿瘤复发和肺转移（P < 0.05），从而延长生存期（P < 0.05） ）。潜在机制分析表明，抗CTLA-4和抗PD-1联合可协同促进CD8+和CD4+ T细胞向肿瘤浸润（P < 0.05 vs.单一抑制剂），从而增强抗肿瘤免疫反应。总之，我们的研究结果表明，抗 CTLA-4 和抗 PD-1 联合免疫疗法可能提供一种新的、有前景的方案，以抑制术后乳腺癌复发和肺转移并改善患者预后，这值得在临床环境中进一步研究。