上皮性卵巢癌 (EOC) 中 T 细胞和抑制性骨髓细胞的存在分别与良好和不良的临床结果相关。这表明 EOC 可能对自体肿瘤浸润淋巴细胞 (TIL) 的过继细胞疗法敏感，前提是骨髓源性抑制细胞和 M2 巨噬细胞的免疫抑制减少。铂类化疗可以缓解这种免疫抑制，可能为基于 T 细胞的免疫治疗创造机会之窗。我们针对在铂类化疗期间接受 TIL 的复发性铂敏感 EOC 患者启动了一项 I/II 期试验 (NCT04072263)。在第二次、第三次和第四次化疗疗程后两周施用 TIL。患者分为两组，分别接受或不使用干扰素-α (IFNa) 作为预处理和 TIL 支持方案。主要终点是根据CTCAE V.4.03标准评估可行性和安全性，次要终点是评估该治疗的临床反应和免疫调节作用。共纳入16名患者。 TIL 可以成功扩展到所有患者。化疗期间不使用 IFNa 的 TIL 治疗 (n=13) 是安全的，但与 IFNa 联合使用会增加化疗引起的毒性，三分之二的患者会出现血小板减少症，这是剂量限制性毒性。 14 名患者完成了完整 TIL 周期的治疗，并进一步评估了临床和免疫反应。铂类化疗导致循环骨髓细胞数量和血浆 IL-6 水平降低，证实了其免疫抑制缓解作用。记录了 3 例完全缓解 (CR)、9 例部分缓解和 2 例疾病稳定，客观缓解率为 86%（实体瘤疗效评估标准 V.1.1）。有趣的是，两名患者的无进展生存期超过了之前的无铂治疗间隔，其中一名患者的 CR 持续时间非常长，同时免疫抑制持续缓解。TIL 疗法可以安全地与铂类化疗联合使用，但不与 IFNa 联合使用。化疗介导的免疫抑制减少和两名患者无铂间隔的增加值得进一步探索铂类化疗期间适当定时的 TIL 输注，可能进一步受益于 IL-2 支持，作为 EOC 患者的一种新的治疗选择.© 作者（或其雇主）2023。根据 CC BY-NC 允许重复使用。不得商业再利用。请参阅权利和权限。英国医学杂志出版。

The presence of T cells and suppressive myeloid cells in epithelial ovarian cancer (EOC) correlate with good and bad clinical outcome, respectively. This suggests that EOC may be sensitive to adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TIL), provided that immunosuppression by myeloid-derived suppressor cells and M2 macrophages is reduced. Platinum-based chemotherapy can alleviate such immunosuppression, potentially creating a window of opportunity for T cell-based immunotherapy.We initiated a phase I/II trial (NCT04072263) in patients with recurrent platinum-sensitive EOC receiving TIL during platinum-based chemotherapy. TILs were administered 2 weeks after the second, third and fourth chemotherapy course. Patients were treated in two cohorts with or without interferon-α (IFNa), as conditioning and TIL support regimen. The primary endpoint was to evaluate the feasibility and safety according to CTCAE V.4.03 criteria and the clinical response and immune modulatory effects of this treatment were evaluated as secondary endpoints.Sixteen patients were enrolled. TIL could be successfully expanded for all patients. TIL treatment during chemotherapy without IFNa (n=13) was safe but the combination with IFNa added to the chemotherapy-induced toxicity with 2 out of 3 patients developing thrombocytopenia as dose-limiting toxicity. Fourteen patients completed treatment with a full TIL cycle and were further evaluated for clinical and immunological response. Platinum-based chemotherapy resulted in reduction of circulating myeloid cell numbers and IL-6 plasma levels, confirming its immunosuppression-alleviating effect. Three complete (CR), nine partial responses and two stable diseases were recorded, resulting in an objective response rate of 86% (Response Evaluation Criteria In Solid Tumors V.1.1). Interestingly, progression free survival that exceeded the previous platinum-free interval was detected in two patients, including an exceptionally long and ongoing CR in one patient that coincided with sustained alleviation of immune suppression.TIL therapy can be safely combined with platinum-based chemotherapy but not in combination with IFNa. The chemotherapy-mediated reduction in immunosuppression and the increase in platinum-free interval for two patients warrants further exploration of properly-timed TIL infusions during platinum-based chemotherapy, possibly further benefiting from IL-2 support, as a novel treatment option for EOC patients.© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.