Biology subjects

Labuz, D.

Publications and source records attributed to Labuz, D..

3 recordsLinked to original sources

bioRxiv2026

Immune repertoire profiling reveals extensive clonal expansion of T and B cells in CXCL9-rich niches in sinonasal cancer

Sinonasal cancer (SNC) is a rare and aggressive head and neck cancer with limited therapeutic options and an incompletely defined immune microenvironment. Although histopathology remains central to clinical tumor evaluation, immune profiling typically requires tissue dissociation and therefore loses the spatial relationships that shape antitumor immunity. Here, we combined single-cell RNA-sequencing approaches, spatial transcriptomics and Spatial V(D)J, a technique we recently pioneered, to analyse the cellular, spatial, and clonal architecture of SNC. We found that SNC tumors were marked by a robust T cell infiltration, including substantial proportions of classical tissue resident memory (TRM) and exhausted (TExh) CD8+ T cells. This inflamed phenotype was accompanied by an immense infiltration of suppressive regulatory T (Treg) cells, which differentiated towards a Tbet+CXCR3+ phenotype. Spatially, expanded Treg, CD8 T and B cell clones concentrated within specialized peritumoral immune niches enriched for cancer-associated fibroblasts, CXCL9 tumor-associated macrophages and LAMP3IDO1 dendritic cells. T cell clones occupying these niches were clonally related to those infiltrating epithelial tumor regions, linking lymphoid hubs to the broader tumor immune response. Together, these data identify SNC as an inflamed but highly immunoregulatory tumor type and reveal a spatially organized clonal architecture in which suppressive and cytotoxic lymphocyte states coexist within CXCL9 myeloid niches.

immunology↗

bioRxiv2026

Intratumoral expression of JAML on NK cells is controlled by tumor microenvironment and MHC class I interaction

Junctional adhesion molecule-like (JAML) is an adhesion molecule known to promote T cell activation and T cell-mediated tumor rejection. In the current study, we show that JAML expression is enriched on mouse intratumoral NK cells compared with splenic NK cells. JAML+ NK cells were associated with tissue residency and co-expressed the immune checkpoints PD-1 and LAG3. JAML expression could be induced on splenic NK cells by IL-2 and further enhanced by IL-21. JAML levels were inversely correlated with inhibitory signaling, as NK cells expressing self-recognizing Ly49 receptors had reduced JAML expression, suggesting regulation of JAML expression by MHC class I molecules. Interaction with the JAML ligand CXADR also reduced JAML surface expression, indicating that tumor-mediated membrane stripping may represent a mechanism of immunoediting. Although JAML RNA transcripts were detectable in human NK cells, JAML protein was found only intracellularly. Together, these findings identify the JAML-CXADR interaction as a potential regulatory pathway in NK cell-mediated killing of tumors.

immunology↗

bioRxiv2020

Mucosal-associated invariant T (MAIT) cells mediate protective host responses in sepsis

Sepsis is a systemic inflammatory response to infection and a leading cause of death. Mucosal-associated invariant T (MAIT) cells are innate-like T cells enriched in mucosal tissues that recognize bacterial ligands. We investigated MAIT cells during clinical and experimental sepsis, and their contribution to host responses. In experimental sepsis, MAIT-deficient mice had significantly increased mortality and bacterial load, and reduced tissue-specific cytokine responses. MAIT cells of WT mice expressed lower levels of IFN-{gamma} and IL-17a during sepsis compared to sham surgery, changes not seen in non-MAIT T cells. MAIT cells of patients presenting with sepsis were significantly reduced in frequency, more activated, and had decreased IFN-{gamma} production when stimulated, compared to healthy donors and paired 90-day post-sepsis samples. Our data suggest that MAIT cells are highly activated and become dysfunctional during clinical sepsis, and contribute to tissue-specific cytokine responses that are protective against mortality during experimental sepsis.

physiology↗