An unconventional integrin promotes human immunityAn unconventional integrin promotes human immunity

ABSTRACT: Cancer remains one of the leading causes of mortality worldwide, with increasing public health interest towards immunological-based approach in disease treatments. Enrichment of certain cell population, namely the CD103+ tissue-resident memory T (Trm) cells has been associated with better clinical prognosis in cancer as well as other inflammatory-diseased patients. However, the identity of specific biomarkers and mechanisms that can contribute towards protective immunity remains unclear. Here, we identified an unexpected CD61 expression on human cancer-specific CD103+ T cells, which formed unconventional transient pairing with CD103 on the synaptic microclusters following antigen recognition, through proteomics, synaptic microscopy and co-immunoprecipitation analyses. Further CD61 co-localisation with T cell receptor (TCR) at the synaptic centre demonstrated modulation of TCR signalling through specific adaptor proteins, which improves anti-tumor cytotoxicity and promote better physiological control of tumor growths in immunocompromised mouse model. Clinically, presence of CD61+ Trm cells are associated with improved patients’ outcome, mediated through enhanced effector functions and phenotypes whilst mitigating hallmarks of cellular exhaustion. This study identified an unconventional and transient CD61 expression and pairing with CD103 on human immune cells, which acts as an important pathway to mediate effective immunity, implicating a novel target for immune-based cellular therapies.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): T Cell, T-lymphocyte Cell Line

SUBMITTER: Adan Pinto-Fernandez  

LAB HEAD: Adan Pinto-Fernandez

PROVIDER: PXD045989 | Pride | 2024-07-30

REPOSITORIES: Pride