Dong Yuexin, Hu Xinyang, Xie Shixin, Song Yuxian, He Yijia, Jin Wanyong, Ni Yanhong, Wang Zhiyong, Ding Liang
Central Laboratory of Stomatology, Affiliated Hospital of Medical School, Nanjing Stomatological Hospital, Nanjing University, Nanjing, China.
Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Medical School, Nanjing Stomatological Hospital, Nanjing University, Nanjing, China.
Front Cell Dev Biol. 2023 Sep 28;11:1257314. doi: 10.3389/fcell.2023.1257314. eCollection 2023.
We previously reported that stroma cells regulate constitutive and inductive PD-L1 (B7-H1) expression and immune escape of oral squamous cell carcinoma. ICOSLG (B7-H2), belongs to the B7 protein family, also participates in regulating T cells activation for tissue homeostasis via binding to ICOS and inducing ICOS T cell differentiation as well as stimulate B-cell activation, while it appears to be abnormally expressed during carcinogenesis. Clarifying its heterogeneous clinical expression pattern and its immune landscape is a prerequisite for the maximum response rate of ICOSLG-based immunotherapy in a specific population. This retrospective study included OSCC tissue samples (n = 105) to analyze the spatial distribution of ICOSLG. Preoperative peripheral blood samples (n = 104) and independent tissue samples (n = 10) of OSCC were collected to analyze the changes of immunocytes (T cells, B cells, NK cells and macrophages) according to ICOSLG level in different cellular contents. ICOSLG is ubiquitous in tumor cells (TCs), cancer-associated fibroblasts (CAFs) and tumor infiltrating lymphocytes (TILs). Patients with high ICOSLGTCs or TILs showed high TNM stage and lymph node metastasis, which predicted a decreased overall or metastasis-free survival. This sub-cohort was featured with diminished CD4 T cells and increased Foxp3+ cells in invasive Frontier , and increased absolute numbers of CD3CD4 and CD8 T cells in peripheral blood. ICOSLG also positively correlated with other immune checkpoint molecules (PD-L1, CSF1R, CTLA4, IDO1, IL10, PD1). Tumor cell-derived ICOSLG could be an efficient marker of OSCC patient stratification for precision immunotherapy.
我们之前报道过，基质细胞可调节组成性和诱导性程序性死亡配体1（PD-L1，B7-H1）的表达以及口腔鳞状细胞癌的免疫逃逸。诱导性共刺激分子配体（ICOSLG，B7-H2）属于B7蛋白家族，它也通过与诱导性共刺激分子（ICOS）结合、诱导ICOS T细胞分化以及刺激B细胞活化来参与调节T细胞活化以维持组织稳态，而它在肿瘤发生过程中似乎存在异常表达。明确其异质性临床表达模式及其免疫格局是在特定人群中基于ICOSLG的免疫治疗实现最大缓解率的前提条件。这项回顾性研究纳入了105例口腔鳞状细胞癌组织样本，以分析ICOSLG的空间分布。收集了104例口腔鳞状细胞癌患者的术前外周血样本和10例独立组织样本，以根据不同细胞成分中ICOSLG水平分析免疫细胞（T细胞、B细胞、NK细胞和巨噬细胞）的变化。ICOSLG在肿瘤细胞（TCs）、癌症相关成纤维细胞（CAFs）和肿瘤浸润淋巴细胞（TILs）中普遍存在。ICOSLG在TCs或TILs中高表达的患者具有较高的TNM分期和淋巴结转移，这预示着总生存期或无转移生存期降低。该亚组的特征是侵袭前沿的CD4 T细胞减少、Foxp3+细胞增加，以及外周血中CD3CD4和CD8 T细胞的绝对数量增加。ICOSLG还与其他免疫检查点分子（PD-L1、集落刺激因子1受体（CSF1R）、细胞毒性T淋巴细胞相关蛋白4（CTLA4）、吲哚胺2,3-双加氧酶1（IDO1）、白细胞介素10（IL10）、程序性死亡受体1（PD1））呈正相关。肿瘤细胞来源的ICOSLG可能是用于精准免疫治疗的口腔鳞状细胞癌患者分层的有效标志物。
