揭示食管基底样鳞状细胞癌与传统食管鳞状细胞癌免疫微环境特征的差异。

Unravelling the difference of immune microenvironment characteristics between esophageal basaloid squamous cell carcinoma and conventional esophageal squamous cell carcinoma.

作者信息

Jiang Dongxian, Xiao Yuhao, Yu Zixiang, Deng Minying, Song Qi, Huang Jie, Su Jieakesu, Xu Chen, Hou Yingyong

机构信息

Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200032, PR China.

出版信息

Hum Pathol. 2025 Jan;155:105716. doi: 10.1016/j.humpath.2025.105716. Epub 2025 Jan 8.

DOI:10.1016/j.humpath.2025.105716

PMID:39793931

Abstract

OBJECTIVES

Esophageal basaloid squamous cell carcinoma (basaloid ESCC) is an uncommon variant of esophageal squamous cell carcinoma (ESCC). We characterized the tumor immune microenvironment features of basaloid ESCC, and compared them with conventional ESCC.

METHODS AND RESULTS

One hundred and four basaloid ESCC patients and 55 conventional ESCC patients were included in Cohort 1. Among 104 basaloid ESCC, 81 were pure basaloid ESCC, and 23 were mixed basaloid ESCC with invasive basaloid ESCC components and ESCC components. In pure basaloid ESCC, there were more immature desmoplastic reaction (P < 0.001), fewer peritumoral tertiary lymphoid structures (TLSs) (P < 0.001), and lower tumor proportional score (TPS) and combined positive score (CPS) (P < 0.001 and P = 0.004) than in conventional ESCC. In mixed basaloid ESCC, the number of mature or intermediate desmoplastic reaction (P < 0.001), the tumor-infiltrating lymphocytes (TILs) score (P = 0.043), the proportion of stromal CD8 TILs (P = 0.047), the number of intratumoral CD20 TILs (P < 0.001), the number of peritumoral TLSs (P = 0.001), the number of peritumoral matureTLSs (P = 0.021), and the PD-L1 (22C3) CPS (P = 0.016) were lower in the basaloid ESCC components than in the conventional ESCC components. In addition, the data of 141 ESCC patients with neoadjuvant chemoimmunotherapy (nICT) were collected to compare immunotherapeutic outcomes. Among 141 nICT-treated patients, 115 patients had residual tumor cells remaining, including 101 with conventional ESCC and 11 with basaloid ESCC. In basaloid ESCC, 18.2% patients had less than 10% residual viable tumor in the esophageal wall (effective response), which was lower than 58.6% in conventional ESCC (P = 0.025).

CONCLUSIONS

Our data indicated that basaloid ESCC had less benefits from immunotherapy than conventional ESCC, and manifested as immune "cold" with immature-type desmoplastic reaction, lower TILs, lower peritumoral TLSs, and lower PD-L1 expression than conventional ESCC.

摘要

目的

食管基底样鳞状细胞癌（基底样食管鳞癌）是食管鳞状细胞癌（食管鳞癌）的一种罕见变体。我们对基底样食管鳞癌的肿瘤免疫微环境特征进行了表征，并将其与传统食管鳞癌进行了比较。

方法与结果

队列1纳入了104例基底样食管鳞癌患者和55例传统食管鳞癌患者。在104例基底样食管鳞癌中，81例为纯基底样食管鳞癌，23例为混合基底样食管鳞癌，包含浸润性基底样食管鳞癌成分和食管鳞癌成分。在纯基底样食管鳞癌中，与传统食管鳞癌相比，未成熟的促结缔组织增生反应更多（P < 0.001），瘤周三级淋巴结构（TLSs）更少（P < 0.001），肿瘤比例评分（TPS）和联合阳性评分（CPS）更低（P < 0.001和P = 0.004）。在混合基底样食管鳞癌中，基底样食管鳞癌成分中的成熟或中间促结缔组织增生反应数量（P < 0.001）、肿瘤浸润淋巴细胞（TILs）评分（P = 0.043）、基质CD8 TILs比例（P = 0.047）、瘤内CD20 TILs数量（P < 0.001）、瘤周TLSs数量（P = 0.001）、瘤周成熟TLSs数量（P = 0.021）以及PD-L1（22C3）CPS（P = 0.016）均低于传统食管鳞癌成分。此外，收集了141例接受新辅助化疗免疫治疗（nICT）的食管鳞癌患者的数据以比较免疫治疗效果。在141例接受nICT治疗的患者中，115例患者有残留肿瘤细胞，其中101例为传统食管鳞癌，11例为基底样食管鳞癌。在基底样食管鳞癌中，18.2%的患者食管壁内残留存活肿瘤少于10%（有效反应），低于传统食管鳞癌的58.6%（P = 0.025）。