采用免疫检查点阻断治疗的林奇综合征患者的肿瘤风险。
Neoplasia risk in patients with Lynch syndrome treated with immune checkpoint blockade.
发表日期：2023 Oct
作者：
Emily C Harrold, Michael B Foote, Benoit Rousseau, Henry Walch, Yelena Kemel, Allison L Richards, Fergus Keane, Andrea Cercek, Rona Yaeger, Dana Rathkopf, Neil H Segal, Zalak Patel, Anna Maio, Matilde Borio, Eileen M O'Reilly, Diane Reidy, Avni Desai, Yelena Y Janjigian, Yonina R Murciano-Goroff, Maria I Carlo, Alicia Latham, Ying L Liu, Michael F Walsh, David Ilson, Jonathan E Rosenberg, Arnold J Markowitz, Martin R Weiser, Anthony M Rossi, Chad Vanderbilt, Diana Mandelker, Chaitanya Bandlamudi, Kenneth Offit, Michael F Berger, David B Solit, Leonard Saltz, Jinru Shia, Luis A Diaz, Zsofia K Stadler
来源：
NATURE MEDICINE
摘要：
转移性和局部错配修复缺陷 (dMMR) 肿瘤对免疫检查点阻断 (ICB) 极其敏感。 ICB 预防 Lynch 综合征 (LS) 患者发生 dMMR 恶性或恶变前肿瘤发展的能力尚不清楚。在 172 名接受 ≥1 个 ICB 周期的癌症患者中，21 名 (12%) 在 ICB 暴露后出现后续恶性肿瘤，其中 91% (29/32) 为 dMMR，中位发展时间为 21 个月（四分位数间）范围，6-38）。随后接受监测结肠镜检查的 61 名 ICB 治疗患者中，有 24 名 (39%) 患有癌前息肉。在匹配的 ICB 前和 ICB 后随访期内，肿瘤发展的总体速率没有变化；然而，在亚组分析中，观察到 ICB 后内脏肿瘤的发生率有所下降。这些数据表明，ICB 治疗 LS 相关肿瘤并不能消除新肿瘤形成的风险，并且 LS 特异性监测策略应继续下去。这些数据对免疫预防策略具有重要意义，并提供对 dMMR 肿瘤免疫生物学的深入了解。© 2023。作者获得 Springer Nature America, Inc. 的独家许可。
Metastatic and localized mismatch repair-deficient (dMMR) tumors are exquisitely sensitive to immune checkpoint blockade (ICB). The ability of ICB to prevent dMMR malignant or pre-malignant neoplasia development in patients with Lynch syndrome (LS) is unknown. Of 172 cancer-affected patients with LS who had received ≥1 ICB cycles, 21 (12%) developed subsequent malignancies after ICB exposure, 91% (29/32) of which were dMMR, with median time to development of 21 months (interquartile range, 6-38). Twenty-four of 61 (39%) ICB-treated patients who subsequently underwent surveillance colonoscopy had premalignant polyps. Within matched pre-ICB and post-ICB follow-up periods, the overall rate of tumor development was unchanged; however, on subgroup analysis, a decreased incidence of post-ICB visceral tumors was observed. These data suggest that ICB treatment of LS-associated tumors does not eliminate risk of new neoplasia development, and LS-specific surveillance strategies should continue. These data have implications for immunopreventative strategies and provide insight into the immunobiology of dMMR tumors.© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.