AUTHOR=Dong Yuexin , Hu Xinyang , Xie Shixin , Song Yuxian , He Yijia , Jin Wanyong , Ni Yanhong , Wang Zhiyong , Ding Liang 

TITLE=ICOSLG-associated immunological landscape and diagnostic value in oral squamous cell carcinoma: a prospective cohort study

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=11

YEAR=2023

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2023.1257314

DOI=10.3389/fcell.2023.1257314

ISSN=2296-634X

ABSTRACT=<p><bold>Background:</bold> 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<sup>+</sup> 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.</p><p><bold>Methods:</bold> 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.</p><p><bold>Results:</bold> 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<sup>+</sup> T cells and increased Foxp3+ cells in invasive Frontier <italic>in situ</italic>, and increased absolute numbers of CD3<sup>+</sup>CD4<sup>+</sup> and CD8<sup>+</sup> T cells in peripheral blood. ICOSLG also positively correlated with other immune checkpoint molecules (PD-L1, CSF1R, CTLA4, IDO1, IL10, PD1).</p><p><bold>Conclusion:</bold> Tumor cell-derived ICOSLG could be an efficient marker of OSCC patient stratification for precision immunotherapy.</p>