May 21, 2014

Antigen-presenting fibroblasts sustain anti-tumour CD4+ T cells in situ via MHCIIp-TCR and C1q-C1qbp binding.

BioRxiv : the Preprint Server for Biology
Sebastian Gil Anthony KonietznyMaria Tsoumakidou

Abstract

In situ antigen presentation is required to sustain active proliferating CD4+ T cells in tumours and to help form memory CD8+ T cells, but the antigen presenting cells (APCs) and pathways involved remain elusive. Cancer associated fibroblasts (CAFs) are prominent stromal constituent of solid tumors. Current immunological dogma considers that CAFs facilitate tumour immune escape. A new subset of MHCII antigen presenting cancer-associated fibroblasts (apCAFs) has been described, but their function remains unknown. Here we report a previously unrecognized function of apCAFs in sustaining CD4+ T cells in primary human and murine lung tumours. In response to IFNγ and oxidative stress in tumours CAFs up-regulated MHCII. Fibroblast-specific targeted ablation of MHCII induced a hypometabolic hypoproliferative state in CD4+ T cells, which impacted MHCII and MHCI immunity, accelerating tumor growth. apCAFs directly presented MHCII-peptide (MCHIIp) complexes to activate the TCRs of CD4+ T cell. Highthrough-put profiling and blocking assays unveiled a novel CAF to T cell communication pathway via complement 1q binding on membrane C1qbp. Thus, apCAFs sustain anti-tumor CD4+ T cells via MHCIIp-TCR and C1q-C1qbp binding. Our studies pave the ...Continue Reading

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Mentioned in this Paper

Microorganism
Biochemical Pathway
Patterns
lignocellulose
Meta Analysis (Statistical Procedure)
Genome
Genes
Enzymes, antithrombotic
Pectins
Cell Wall Macromolecule Catabolic Process

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