与术前化疗的病理反应相比,结直肠肝转移病灶间的免疫特征的均一性更能够更准确地鉴别出具有良好预后的患者。
Homogeneity in immune features between colorectal liver metastases better identifies patients with good prognosis compared to pathological response to preoperative chemotherapy.
发表日期:2023
作者:
David Henault, David Stephen, Pierre-Antoine St-Hilaire, Nouredin Messaoudi, Franck Vandenbroucke-Menu, Eve Simoneau, Zhixia Rong, Marylène Plasse, Richard Létourneau, André Roy, Michel Dagenais, Réal Lapointe, Bich Nguyen, Anne-Marie Mes-Masson, G Soucy, Simon Turcotte
来源:
Immunity & Ageing
摘要:
结直肠癌肝转移(CRLM)中,肿瘤浸润淋巴细胞密度、I类主要组织相容性复合物(MHC-I)的表达以及术前化疗的病理反应与完全切除后的肿瘤学结果相关联。然而,对于多发性CRLM患者中这些特征的异质性的预后意义仍在调查中。我们使用了一个包含220个基因匹配修复-基因熟练的CRLM的组织微阵列,在97名患者中进行了前瞻性随访,通过免疫组织化学法定量CD3+ T细胞和MHC-I。使用标准评分系统评估术前化疗的组织病理学反应。我们测试了临床、免疫学和病理学特征与肿瘤学结果之间的关联。总体而言,29名患者(30.2%)具有CD3+ T细胞浸润和MHC-I均匀的CRLMs。与异质性CRLMs相比,免疫均匀的患者具有更长的中位无复发时间(TTR)(30 vs 12个月,P =.0018)和疾病特异性存活(DSS)(未达到vs 48个月,P =.0009)。在6年内,80%的免疫均一的CRLM患者仍然存活。根据不同的分级系统,60例(61.9%)和69例(80.2%)患者的术前化疗反应均匀。与TTR或DSS无关。CD3和MHC-I的异质性对于术前化疗的反应以及与肿瘤学结果的其他临床病理学变量的关联是独立的。在以治疗为目的切除多发性CRLM的患者中,肿瘤异质一致的自适应免疫特征可能比术前化疗的病理反应更有预测肿瘤学结果的信息价值。© 2023 The Author(s). Published with license by Taylor & Francis Group, LLC.
In colorectal cancer liver metastases (CRLM), the density of tumor-infiltrating lymphocytes, the expression of class I major histocompatibility complex (MHC-I), and the pathological response to preoperative chemotherapy have been associated with oncological outcomes after complete resection. However, the prognostic significance of the heterogeneity of these features in patients with multiple CRLMs remains under investigation. We used a tissue microarray of 220 mismatch repair-gene proficient CRLMs resected in 97 patients followed prospectively to quantify CD3+ T cells and MHC-I by immunohistochemistry. Histopathological response to preoperative chemotherapy was assessed using standard scoring systems. We tested associations between clinical, immunological, and pathological features with oncologic outcomes. Overall, 29 patients (30.2%) had CRLMs homogeneous for CD3+ T cell infiltration and MHC-I. Patients with immune homogeneous compared to heterogeneous CRLMs had longer median time to recurrence (TTR) (30 vs. 12 months, p = .0018) and disease-specific survival (DSS) (not reached vs. 48 months, p = .0009). At 6 years, 80% of the patients with immune homogeneous CRLMs were still alive. Homogeneity of response to preoperative chemotherapy was seen in 60 (61.9%) and 69 (80.2%) patients according to different grading systems and was not associated with TTR or DSS. CD3 and MHC-I heterogeneity was independent of response to pre-operative chemotherapy and of other clinicopathological variables for their association with oncological outcomes. In patients with multiple CRLMs resected with curative intent, similar adaptive immune features seen across metastases could be more informative than pathological response to pre-operative chemotherapy in predicting oncological outcomes.© 2023 The Author(s). Published with license by Taylor & Francis Group, LLC.