Spatially resolved transcriptomics reveal the determinants of primary resistance to immunotherapy in NSCLC with mature tertiary lymphoid structures.

• Tác giả: Alban Bessede, Maxime Brunet, Emma Clot, Jean-Michel Coindre, Marie Del Castillo, Thomas Grellety, Jean-Philippe Guégan, Antoine Italiano, Robert J Johnston, Oren Lara, Sylvestre Le Moulec, Ophélie Odin, Florent Peyraud, Christophe Rey, Angélique Tasseel, Lucile Vanhersecke
• Ngôn ngữ: eng
• Thông tin xuất bản: United States : Cell reports. Medicine , 2025
• Bộ sưu tập: NCBI
• ID: 679727

Tóm tắt

Effectiveness of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) has been linked to the presence of mature tertiary lymphoid structures (mTLSs) within the tumor microenvironment (TME). However, only a subset of mTLS-positive NSCLC derives benefit, thus highlighting the need to unravel ICI response determinants. The comprehensive analysis of ICI-treated patients with NSCLC (n = 509) from the Bergonié Institute Profiling (BIP) study (NCT02534649) reveals that the presence of mTLSs correlates with improved clinical outcomes, independently of programmed death ligand 1 (PD-L1) expression and genomic features. Employing spatial transcriptomics alongside multiplex immunofluorescence (mIF), we show that two distinct subsets of cancer-associated fibroblasts (CAFs) are essential factors in mediating primary resistance to ICIs in mTLS-positive NSCLC. These CAFs are associated with immune exclusion, CD8