biostudies-literatureDi Modugno FAssociazione Italiana per la Ricerca sul CancroMinistero della SaluteACCAccident Compensation CorporationNCI NIH HHSCancer Research InstituteFondazione Italiana per la Ricerca sul Cancro AircChulabhorn Research Institute105003https://www.ebi.ac.uk/biostudies/studies/S-EPMC10869748biostudies-literatureUnknown101<h4>Background</h4>Tertiary Lymphoid Structures (TLS) correlate with positive outcomes in patients with NSCLC and the efficacy of immune checkpoint blockade (ICB) in cancer. The actin regulatory protein hMENA undergoes tissue-specific splicing, producing the epithelial hMENA^11a linked to favorable prognosis in early NSCLC, and the mesenchymal hMENAΔv6 found in invasive cancer cells and pro-tumoral cancer-associated fibroblasts (CAFs). This study investigates how hMENA isoforms in tumor cells and CAFs relate to TLS presence, localization and impact on patient outcomes and ICB response.<h4>Methods</h4>Methods involved RNA-SEQ on NSCLC cells with depleted hMENA isoforms. A retrospective observational study assessed tissues from surgically treated N0 patients with NSCLC, using immunEBioMedicineTumoral and stromal hMENA isoforms impact tertiary lymphoid structure localization in lung cancer and predict immune checkpoint blockade response in patients with cancer.PMC10869748R37 CA247676IG 19822RCR-2019-23669120Xiong JNistico PPalermo BCappuzzo FVincent BGWarren SVisca PD'Ambrosio LGoeman FDe Nicola FPanetta MFacciolo FBalzano VWheeler NMelchionna RD'Andrea DGallo EBortone DSDi Carlo ACampo GTripodo CSperduti IAntoniani BLambrechts DCarpano SBelmonte BFrige GDi Modugno FGallina FSpada SMorello GfalseTumoral and stromal hMENA isoforms impact tertiary lymphoid structure localization in lung cancer and predict immune checkpoint blockade response in patients with cancer.<h4>Background</h4>Tertiary Lymphoid Structures (TLS) correlate with positive outcomes in patients with NSCLC and the efficacy of immune checkpoint blockade (ICB) in cancer. The actin regulatory protein hMENA undergoes tissue-specific splicing, producing the epithelial hMENA^11a linked to favorable prognosis in early NSCLC, and the mesenchymal hMENAΔv6 found in invasive cancer cells and pro-tumoral cancer-associated fibroblasts (CAFs). This study investigates how hMENA isoforms in tumor cells and CAFs relate to TLS presence, localization and impact on patient outcomes and ICB response.<h4>Methods</h4>Methods involved RNA-SEQ on NSCLC cells with depleted hMENA isoforms. A retrospective observational study assessed tissues from surgically treated N0 patients with NSCLC, using immun2024-01-01T00:00:00Z2024 Mar2026-06-12T05:50:38.705Z2025-04-05T09:07:58.87ZS-EPMC108697483834055710.1016/j.ebiom.2024.105003