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Thrombospondin-1–CD47 signaling contributes to the development of T cell exhaustion in cancer

Merghoub, Wolchok and colleagues reveal a role of the extracellular matrix protein thrombospondin-1 (TSP-1) and CD47 in promoting T cell exhaustion during tumor progression in mice and humans.

Chien-Huan Weng
Anais Assouvie
Taha Merghoub
Research17 Nov 2025
Nature Immunology

Volume: 26, P: 2296-2311
Blockade of the AHR restricts a Treg-macrophage suppressive axis induced by L-Kynurenine

The tryptophan metabolite kynurenine is an endogenous ligand of the aryl hydrocarbon receptor (AHR). Here, the authors show that AHR targeting in IDO/TDO-expressing tumours counteracts a regulatory T cell/macrophage suppressive axis and synergizes with immune checkpoint blockade to hinder tumour growth.

Luis Felipe Campesato
Sadna Budhu
Jedd D. Wolchok
ResearchOpen Access11 Aug 2020
Nature Communications

Volume: 11, P: 1-11
MHC-I expression renders catecholaminergic neurons susceptible to T-cell-mediated degeneration

MHC-I is expressed in neurons where it is implicated in synaptic plasticity and neuron regeneration. Here, Cebrián et al. report an increase in MHC-I expression in brain neurons from Parkinson’s disease patients, which is triggered by microglial activation and circulating dopamine.

Carolina Cebrián
Fabio A. Zucca
David Sulzer
Research16 Apr 2014
Nature Communications

Volume: 5, P: 1-14
Apoptotic contraction drives target cell release by cytotoxic T cells

To kill target cells, cytotoxic T lymphocytes (CTLs) form an immune synapse (IS) to elicit cell death and the IS then dissolves to allow for CTL serial killing. Huse et al. find that IS dissolution occurs concomitantly with cytoskeletal contraction of apoptotic targets and this is both necessary and sufficient for CTL dissociation

Elisa E. Sanchez
Maria Tello-Lafoz
Morgan Huse
Research27 Jul 2023
Nature Immunology

Volume: 24, P: 1434-1442
Rational design of anti-GITR-based combination immunotherapy

GITR agonism can be exploited in combination with checkpoint blockade to overcome immune refractoriness in solid tumors.

Roberta Zappasodi
Cynthia Sirard
Taha Merghoub
Research29 Apr 2019
Nature Medicine

Volume: 25, P: 759-766
Overcoming resistance to checkpoint blockade therapy by targeting PI3Kγ in myeloid cells

Targeting tumour-infiltrating suppressive myeloid cells with a selective PI3Kγ inhibitor overcomes resistance to checkpoint blockade therapy in various mouse myeloid-rich tumour models.

Olivier De Henau
Matthew Rausch
Taha Merghoub
Research09 Nov 2016
Nature

Volume: 539, P: 443-447
Isoform specific anti-TGFβ therapy enhances antitumor efficacy in mouse models of cancer

Gupta et al. demonstrate that targeting isoform-specific TGFβ leads to an increase in the anti-tumor response when compared to pan-TGFβ inhibition, due to enhanced CD8 T cell function. The authors also report that combining TGFβ inhibition with immune checkpoint blockade results in improved tumor control.

Aditi Gupta
Sadna Budhu
Taha Merghoub
ResearchOpen Access17 Nov 2021
Communications Biology

Volume: 4, P: 1-14
Neoadjuvant vascular-targeted photodynamic therapy improves survival and reduces recurrence and progression in a mouse model of urothelial cancer

Barak Rosenzweig
Renato B. Corradi
Jonathan A. Coleman
ResearchOpen Access01 Mar 2021
Scientific Reports

Volume: 11, P: 1-13

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