Data from Spatial and Single-Cell Transcriptomics Reveal a Cancer-Associated Fibroblast Subset in HNSCC That Restricts Infiltration and Antitumor Activity of CD8⁺ T Cells

• DOI: 10.1158/0008-5472.c.7027357.v1
• Publication Date: 2024-01-16T08:23:16Z
• Authors: Chuwen Li; Haiyan Guo; Peisong Zhai; Ming Yan; Chun Liu; Xiaoning Wang; Chaoji Shi; Jiang Li; Tong Tong; Zhiyuan Zhang; Hailong Ma; Jianjun Zhang
• Keywords: Tumor-infiltrating lymphocytes

<div>Abstract<p>Although immunotherapy can prolong survival in some patients with head and neck squamous cell carcinoma (HNSCC), the response rate remains low. Clarification of critical mechanisms regulating CD8<sup>+</sup> T-cell infiltration dysfunction tumor microenvironment could help maximize benefit for treating HNSCC. Here, we performed spatial transcriptomic analysis HNSCC specimens differing immune single-cell RNA sequencing five pairs adjacent tissues, revealing specific cancer-associated fibroblast (CAF) subsets related to restriction dysfunction. These CAFs exhibited high expression CXCLs (CXCL9, CXCL10, CXCL12) MHC-I enrichment galectin-9 (Gal9). The proportion MHC-I<sup>hi</sup>Gal9<sup>+</sup> was inversely correlated abundance a TCF1<sup>+</sup>GZMK<sup>+</sup> subset T cells. Gal9 on induced decreased tumor-infiltrating TCF1<sup>+</sup>CD8<sup>+</sup> Collectively, identification advances understanding precise role cancer evasion paves way more effective HNSCC.</p>Significance:<p>Spatial identifies IFN-induced that form trap cells, providing insights into complex networks regulate function.</p></div>