Year: 2026
Type: preprint
Abstract: ABSTRACT Cancer immunosurveillance largely relies on effector CD8 + T cells, yet surface determinants of cytotoxic competence within tumor-reactive populations remain incompletely defined. Using single-cell surface proteomics in a mouse breast cancer model, we identified a tumor-enriched subset of antigen-experienced CD8 + T cells expressing CD11b, a prototypic myeloid integrin. CD11b⁺ CD8⁺ T cells were detected across mouse tumor models and human solid tumors and, within tumor-reactive populations, CD11b marked cells with greater cytotoxic potential. Following activation, naive CD8 + T cells induced ITGAM transcription and CD18-dependent CD11b surface expression. Mechanistically, CD11b localized to the peripheral adhesive ring of the immune synapse and promoted lytic-granule secretion. Accordingly, CD11b + T cells exhibited enhanced TCR- and CAR-mediated tumor cell killing, whereas CD11b deletion impaired T cell antitumor activity. Together, these findings identify CD11b as an inducible, noncanonical component of the T cell immune synapse that marks cytotoxic competence and promotes antitumor T cell function.
Authors: Jone Etxaniz-Diaz de Durana, Alexandre Bosch, Endika Prieto-Fernández, Lorena Pérez-Gutiérrez, Kexin Yu, Paloma Velasco-Beltrán, Leire Egia-Mendikute, Iker Oyenarte, So Young Lee, Ander de Blas, Iñaki Eguren-Santamaría, Jesús Jiménez-Barbero, Miguel F Sanmamed, Maria M Caffarel, Ana M. Aransay, Alena Gros, Pablo F. Cespedes, Asis Palazon, June Ereño-Orbea, Asier Antoñana-Vildosola
Institutions: CIC bioGUNE, Vall d'Hebron Institute of Oncology, Chinese Academy of Medical Sciences & Peking Union Medical College, University of Oxford, Navarre Institute of Health Research, Clinica Universidad de Navarra, Centro de Investigación Médica Aplicada, Ikerbasque, University of the Basque Country, Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, Biogipuzkoa Health Research Institute, Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Funders: Fundación BBVA, Fundación Ramón Areces, Mizutani Foundation for Glycoscience, Ministerio de Ciencia, Innovación y Universidades, European Commission, Fundación Científica Asociación Española Contra el Cáncer, Fundación Fero, Instituto de Salud Carlos III, Agencia Estatal de Investigación, NextGenerationEU
Awards: G1096179202, G1105844351, G1228417121, G1272900390, G1968358523, G2062341269, G214811770, G2612339722, G2839357914, G318412399, G3969365381, G4212894969, G4508456733, G4688950647, G491712853, G4935322834, G5131721712, G5404395142, G5635532810, Identificación de antígenos tumorales no canónicos y análisis de su relevancia en la inmunoterapia del cáncer: inmunogenicidad, valor predictivo y potencial terapeútico, G624877701, G6520718613, G6731524417, G7216601661, G7395345766, G7744275217, G7805098552, G7805626310, G7863371703, G8497050386, G8667377315
OpenAlex ID: W7221922385