Rahul Roychoudhuri

The Roychoudhuri group has relocated to the University of Cambridge Department of Pathology where Rahul Roychoudhuri has taken up a University Senior Lectureship as of June 1st 2020. Visit the Roychoudhuri Group webpage for full details of the group's current research.

Immunoregulation: Uncovering the 'brakes' on immune activation CD4+ and CD8+ T cells have a powerful ability to drive immune activation and promote clearance of infections and cancer. However, their function can also promote deleterious autoimmune and allergic inflammation. The immune system therefore employs a variety of suppressive mechanisms, collectively referred to as immunoregulatory mechanisms, to restrain excessive immune activation.

While immunoregulatory mechanisms play a beneficial role in preventing inflammation, they can also powerfully suppress immune responses during chronic infections and cancer in a process referred to as immunosuppression. Immunoregulatory mechanisms therefore function as 'brakes' on immune activation and are important therapeutic targets.

Our research aims to understand the molecular and cellular mechanisms of tolerance and immunosuppression in physiology, and during infection, inflammation and cancer. We hope that this will enable development of new therapies aimed at manipulating immune function in patients with inflammation and cancer.

 

Latest Publications

IRF4 instructs effector Treg differentiation and immune suppression in human cancer.
Alvisi G, Brummelman J, Puccio S, Mazza EMC, Paoluzzi Tomada E, Losurdo A, Zanon V, Peano C, Colombo FS, Scarpa A, Alloisio M, Vasanthakumar A, Roychoudhuri R, Kallikourdis M, Pagani M, Lopci E, Novellis P, Blume J, Kallies A, Veronesi G, Lugli E

The molecular mechanisms responsible for the high immunosuppressive capacity of CD4+ regulatory T cells (Tregs) in tumors are poorly known. High-dimensional single cell profiling of T cells from chemotherapy-naïve individuals with non-small cell lung cancer identified the transcription factor IRF4 as specifically expressed by a subset of intratumoral CD4+ effector Tregs with superior suppressive activity. In contrast to the IRF4- counterparts, IRF4+ Tregs expressed a vast array of suppressive molecules, and their presence correlated with multiple exhausted subpopulations of T cells. Integration of transcriptomic and epigenomic data revealed that IRF4, either alone or in combination with its partner BATF, directly controlled a molecular program responsible for immunosuppression in tumors. Accordingly, deletion of Irf4 exclusively in Tregs resulted in delayed tumor growth in mice while the abundance of IRF4+ Tregs correlated with poor prognosis in patients with multiple human cancers. Thus, a common mechanism underlies immunosuppression in the tumor microenvironment irrespectively of the tumor type.

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The Journal of clinical investigation, 1, 1, 03 Mar 2020

DOI: 10.1172/JCI130426

PMID: 32125291

Genome-Wide Measurement and Computational Analysis of Transcription Factor Binding and Chromatin Accessibility in Lymphocytes.
Sadiyah MF, Roychoudhuri R

Cells of the adaptive immune system, including CD4 and CD8 T cells, as well as B cells, possess the ability to undergo dynamic changes in population size, differentiation state, and function to counteract diverse and temporally stochastic threats from the external environment. To achieve this, lymphocytes must be able to rapidly control their gene-expression programs in a cell-type-specific manner and in response to extrinsic signals. Such capacity is provided by transcription factors (TFs), which bind to the available repertoire of regulatory DNA elements in distinct lymphocyte subsets to program cell-type-specific gene expression. Here we provide a set of protocols that utilize massively parallel sequencing-based approaches to map genome-wide TF-binding sites and accessible chromatin, with consideration of the unique aspects and technical issues facing their application to lymphocytes. We show how to computationally validate and analyze aligned data to map differentially enriched/accessible sites, identify enriched DNA sequence motifs, and detect the position of nucleosomes adjacent to accessible DNA elements. These techniques, when applied to immune cells, can enhance our understanding of how gene-expression programs are controlled within lymphocytes to coordinate immune function in homeostasis and disease. © 2019 by John Wiley & Sons, Inc.

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Current protocols in immunology, 126, 1934-368X, 2019

PMID: 31483104

Regulatory T cells in cancer: where are we now?
Gallimore A, Quezada SA, Roychoudhuri R

There have been substantial strides forward in our understanding of the contribution of regulatory T (Treg) cells to cancer immunosuppression. In this issue, we present a series of papers highlighting emerging themes on this topic relevant not only to our understanding of the fundamental biology of tumour immunosuppression but also to the design of new immunotherapeutic approaches. The substantially shared biology of CD4 conventional T (Tconv) and Treg cells necessitates a detailed understanding of the potentially opposing functional consequences that immunotherapies will have on Treg and Tconv cells, a prominent example being the potential for Treg-mediated hyperprogressive disease following anti-PD-1 therapy. Such understanding will aid patient stratification and the rational design of combination therapies. It is also becoming clear, however, that Treg cells within tumours exhibit distinct biological features to both Tconv cells and Treg cells in other tissues. These distinct features provide the opportunity for development of targeted immunotherapies with greater efficacy and reduced potential for inducing systemic toxicity.

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Immunology, 157, 1365-2567, 2019

PMID: 31225653