Ribeiro Mauricio Fernando, Demicco Elizabeth G, Razak Albiruni Ryan Abdul
Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
Ther Adv Med Oncol. 2024 May 13;16:17588359241250158. doi: 10.1177/17588359241250158. eCollection 2024.
Intimal sarcoma (InS) is an ultra-rare and aggressive subtype of soft tissue sarcoma (STS). It usually arises in large mediastinal arteries and the heart. In the advanced setting, sequential cytotoxic chemotherapy is often used, mainly based on retrospective studies and case series but with modest benefit. The use of immune checkpoint inhibitors is a promising strategy for some STS, but identifying biomarkers of response remains challenging due to disease rarity and heterogeneity. A reactive and pro-inflammatory tumor microenvironment (TME) is believed to be associated with better outcomes for patients receiving anti-PD-1-based regimens, generating the rationale to explore this strategy in malignancies with this characteristic, such as InS. We report three cases of advanced InS patients experiencing partial response to pembrolizumab-based therapy despite low tumor mutational burden and absence of mismatch-repair deficiency. We hypothesize that TME-related characteristics such as PD-L1 expression and the presence of tertiary lymphoid structures might explain this phenomenon.
内膜肉瘤（InS）是软组织肉瘤（STS）中一种极为罕见且侵袭性强的亚型。它通常发生于大的纵隔动脉和心脏。在晚期情况下，序贯细胞毒性化疗经常被使用，主要基于回顾性研究和病例系列，但获益有限。免疫检查点抑制剂的使用对某些STS来说是一种有前景的策略，但由于疾病罕见性和异质性，确定反应生物标志物仍然具有挑战性。一种反应性和促炎性肿瘤微环境（TME）被认为与接受基于抗PD-1方案的患者更好的预后相关，这为在具有这种特征的恶性肿瘤（如InS）中探索该策略提供了理论依据。我们报告了3例晚期InS患者，尽管肿瘤突变负荷低且不存在错配修复缺陷，但对基于帕博利珠单抗的治疗仍有部分反应。我们推测，TME相关特征如PD-L1表达和三级淋巴结构的存在可能解释了这一现象。
