Biology subjects

Ruhland, M. K.

Publications and source records attributed to Ruhland, M. K..

4 recordsLinked to original sources

bioRxiv2026

Self-antigen disrupts cDC1 mediated antitumor responses

Conventional dendritic cells navigate complex tissues and sample peripheral antigens, balancing immune suppression and activation to achieve tissue homeostasis. However, it remains unclear how an individual dendritic cells reconciles co-incident signals from immunological opposing antigens within the tissue or tumor microenvironment, where tolerogenic self-antigen and immunogenic tumor antigen or microbes coexist. Here, using complementary in vivo fluorescent reporter systems, high-resolution imaging and endosomal profiling, we simultaneously tracked uptake, intracellular processing and cross-presentation of cutaneous self, tumor and microbial antigens in murine skin tissue, tumors and draining lymph nodes. We find that a substantial fraction of dendritic cells acquire antigen from multiple sources and that localization within endosomal compartments is dictated by antigen source. Notably, type 1 conventional dendritic cells that co-process self and tumor antigen represent a significant proportion of tumor antigen-bearing dendritic cells in the tumor and tumor draining lymph node. These dual-antigen loaded dendritic cells display a diminished capacity to prime tumor-specific CD8+ T cells and a marked reduction in tumor derived peptide presented on surface MHCI, while cross-priming of self-antigen specific T cells is significantly increased. These changes occur despite equivalent or greater tumor antigen uptake relative to self-antigen and high expression of surface MHCI and costimulatory molecules. Together, these data support a model in which multiantigen processing within dendritic cells can bias peptide loading away from tumor-derived epitopes, thereby limiting tumor-specific cross-priming. Modulating the antigenic context of the tumor microenvironment or endosomal routing after antigen uptake may therefore represent a strategy to restore effective dendritic cell-mediated antitumor immunity.

immunology↗

bioRxiv2025

Contextual control of CD8+ T cell priming by dendritic cell subsets in tumor and inflammatory microenvironments

Conventional dendritic cells orchestrate adaptive immunity by trafficking peripheral antigens to draining lymph nodes and presenting peptide-MHC complexes to prime naive T cells. Migratory and lymph node resident conventional dendritic cell subsets occupy distinct anatomical niches and have been shown to shape T cell activation in a variety of immunologic contexts including infection, vaccination and cancer. How peripheral tissue context and dendritic cell subset specific transcriptional programs collaborate to determine CD8+ T cell priming remains incompletely defined. Using fluorescent antigen, we tracked antigen distribution, dendritic cell transcriptional programming, and functional cross-presentation across tumor, inflammatory, and steady state tissue contexts. We find that skin tumor antigen is more widely distributed amongst draining lymph node conventional dendritic cells than skin antigen derived from either steady state or inflamed skin tissue. Comparing across dendritic cell subsets, migratory type 1 dendritic cells display higher expression of MHCI antigen presentation machinery and genes associated with cross-presentation compared with lymph node resident type 1 dendritic cells in tumor and inflamed tissue contexts. Similarly, they exhibited superior per-cell cross-presentation and stronger induction of naive CD8+ T cell responses. We find that both antigen access in the lymph node and context-specific cross-presentation efficiency together predict the magnitude and quality of CD8+ T cell priming. These results identify migratory dendritic cells, particularly type 1, as central mediators of antitumor CD8+ T cell responses and support therapeutic strategies that augment the efficiency of resident dendritic cell cross-presentation.

immunology↗

bioRxiv2021

Holistic Characterization of Tumor Monocyte-to-Macrophage Differentiation Integrates Distinct Immune Phenotypes in Kidney Cancer

The tumor immune microenvironment (TIME) is commonly infiltrated by diverse collections of myeloid cells. Yet, the complexity of myeloid cell identity and plasticity has challenged efforts to define bona fide populations and determine their connections to T cell function and their relation to patient outcome. Here we leverage single-cell RNA-sequencing (scRNA-seq) analysis of several mouse and human tumors and find that monocyte-macrophage diversity is characterized by a combination of conserved lineage states as well as transcriptional programs accessed along the differentiation trajectory. Using mouse models, we also find that tumor monocyte-to-macrophage progression is profoundly tied to regulatory T cell (Treg) abundance. Importantly, in human kidney cancer, heterogeneity in macrophage accumulation and myeloid composition corresponded to variance in, not only Treg density, but also the quality of infiltrating CD8+ T cells. In this way, holistic analysis of monocyte-to-macrophage differentiation creates a framework for critically different immune states in kidney tumors.

immunology↗

bioRxiv2019

Tumors Exploit Dedicated Intracellular Vesicles to Program T cell Responses

In order to drive productive tumor-infiltrating lymphocyte (TIL) function, myeloid populations must direct antigens to the lymph node, including to resident antigen-presenting cells (APCs) that have never touched the tumor. It has long been supposed that APCs trade antigens with one another, but the dominant cell biology underlying that remains unknown. We used in vitro and in vivo assays together with lattice light sheet and multiphoton imaging to show that myeloid cells carry tumor antigen-laden vesicles that they trade with one another as they reach distant sites. This accounts for the majority of antigen displayed to T cells and provides tumors with a mechanism to access APCs that differentially direct T cell activation away from memory phenotypes. This work defines efficient cell biology that drives the first steps of TIL generation and represents a new frontier for engineering tumoral immunity.

immunology↗