Biology subjects

Missolo-Koussou, Y.

Publications and source records attributed to Missolo-Koussou, Y..

4 recordsLinked to original sources

bioRxiv2026

The differentiation and functional landscape of tumor-resident CD8⁺ T cells shapes immunity and clinical outcomes in clear cell renal cell carcinoma

Clear cell renal cell carcinoma (ccRCC) is a common and lethal kidney cancer in which CD8+ T cell-targeted immunotherapies are standard of care. However, tumor CD8+ T cell infiltration correlates with divergent clinical outcomes, reflecting functional heterogeneity. We comprehensively characterized tumor-specific memory CD8+ T cells in ccRCC using phenotypic, transcriptional and functional analyses. Three major subsets were identified based on tissue-residency markers: circulating (Tcirc), tissue-resident (Trm) and CD69+CD103- Trm-like cells, all recognizing autologous RCC cells in an HLA class I-dependent manner. Tcirc cells exhibited greater stemness and cytotoxic potential, whereas Trm populations displayed tissue-residency programs, enhanced tumor reactivity and exhaustion features. Single-cell transcriptomics analyses uncovered substantial heterogeneity within Trm cells, including progenitor, activated, transitional, type-17, interferon-responsive, regulatory and terminally exhausted states. Trajectory and TCR analyses indicated progressive differentiation from central-memory Tcirc cells toward tissue residency while losing circulation, cytotoxicity and stemness potentials and then progress toward terminal exhaustion. Enrichment of progenitor Trm cells associated with improved survival and favorable immunotherapy response, whereas regulatory or exhausted Trm cells correlated with poor outcomes. These findings define the differentiation and functional landscape of tumor-specific CD8+ T cells that shapes immunity and clinical outcomes in ccRCC.

immunology↗

bioRxiv2025

Common origin for effector and regulatory Follicular and Tissue-Adapted CD4+ T cells in Non-Small Cell Lung Cancer

Tumor-invaded lymph nodes (LNs) serve as critical hubs for anti-tumor immunity, yet their role in orchestrating immune responses remains poorly understood. Using integrated single-cell RNA sequencing, T cell receptor sequencing, and chromatin accessibility profiling, we analyzed CD4+ T cells from matched blood, tumor-invaded LNs, and tumors of treatment-naive non-small cell lung cancer patients. We identified distinct immunological landscapes across these compartments. Compared to blood, tumor-invaded LNs and tumors were enriched for follicular regulatory T cells (Treg-Tfr), conventional T cell subsets with Tfh-like characteristics (Tconv-Tfh and Tconv-CXCL13), and tissue-resident memory Tregs (Treg-Trm). These populations share a BATF-dependent transcriptional program that governs T-cell activation and tissue adaptation, while simultaneously engaging distinct, subset-specific regulatory networks. Integrative TCR-RNA analysis revealed that tumor-reactive, neoantigen-specific T cell clones were enriched within these subsets and demonstrated extensive LN-tumor clonal sharing, indicating active recirculation between compartments. Through clonal coupling analysis and trajectory inference, we uncovered that Treg-Tfr cells function as multipotent progenitors that bifurcate into tissue-resident Treg-Trm or into ex-Tregs adopting a Tfh-like CXCL13+ ewector phenotype. Remarkably, follicular CD4+ T subsets from LNs and tumor were transcriptionally and epigenetically similar and localized to analogous germinal center niches. These findings establish tumor-invaded LNs as functional extensions of the tumor microenvironment that generate and maintain tumor-reactive CD4+ lineages. The identification of tissue-resident Treg-Tfr plasticity reveals a critical developmental checkpoint that could be therapeutically targeted to redirect immunosuppressive programs toward anti-tumor ewector responses.

immunology↗

bioRxiv2021

Tissue-resident FOLR2+ macrophages associate with tumor-infiltrating CD8+ T cells and with increased survival of breast cancer patients.

Macrophage infiltration is a hallmark of solid cancers and overall macrophage infiltration is correlated with lower patient survival and resistance to therapy. However, tumor-associated macrophages are phenotypically and functionally heterogeneous. Specific tumor-associated macrophage subsets might be endowed with antagonistic role on cancer progression and on the development of anti-tumor immunity. For instance, monocyte-derived TREM2+ tumor-associated macrophages have pro-tumorigenic and immunosuppressive functions. Here, we identify a discrete population of FOLR2+ tumor-associated macrophages positively correlating with patient survival in breast cancer. FOLR2+ macrophages are evolutionarily conserved across species and populate human and murine healthy mammary gland. Moreover, FOLR2+ macrophages co-localize with lymphoid aggregates containing CD8+ T cells in breast cancer and across ten other types of cancers. This study highlights antagonistic roles for tumor-associated macrophage subsets and paves the way for subset-specific therapeutic interventions in macrophages-based cancer therapies.

immunology↗

bioRxiv2019

Engineered niches support the development of human dendritic cells in humanized mice

Classical dendritic cells (cDCs) are rare sentinel cells specialized in the regulation of adaptive immunity. Modeling cDC development is both crucial to study cDCs and harness their potential in immunotherapy. Here we addressed whether cDCs could differentiate in response to trophic cues delivered by mesenchymal components of the hematopoietic niche where they physiologically develop and maintain. We found that expression of the membrane bound form of human FLT3L and SCF together with CXCL12 in a bone marrow mesenchymal stromal cell line is sufficient to induce the contact-dependent specification of both type 1 and type 2 cDCs from CD34+ hematopoietic stem and progenitor cells (HSPCs). Engraftment of these engineered mesenchymal stromal cells (eMSCs) together with CD34+ HSPCs creates an in vivo synthetic niche in the dermis of immunodeficient mice. Cell-to-cell contact between HSPCs and stromal cells within these organoids drive the local specification of cDCs and CD123+AXL+CD327+ pre/AS-DCs. cDCs generated in vivo display higher levels of resemblance with human blood cDCs unattained by in vitro generated subsets. Altogether, eMSCs provide a novel and unique platform recapitulating the full spectrum of cDC subsets enabling their functional characterization in vivo.

immunology↗