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Department of Pathology

 

Immune regulation in inflammation, infection and cancer

The immune system defends us against infections and cancer but can also provoke autoimmune and allergic inflammation. The immune system therefore employs a variety of suppressive mechanisms, known as immunoregulatory mechanisms, to limit inflammation and immune pathology during infection. Immunoregulatory mechanisms also powerfully restrict T cell responses in cancer, resulting in deleterious immunosuppression. Immunoregulatory mechanisms therefore function as ‘brakes’ on immune activation and have important consequences in infection, inflammation and cancer.

Our group's research aims to uncover the molecular and cellular mechanisms underpinning immune regulation and cancer immunosuppression. Fundamental discovery in the field of immune regulation will pave the way for new therapies aimed at manipulating immune function in patients with autoimmunity and cancer.

 

For a full description of our research, visit: http://roychoudhurilab.org/

 

Biography

Rahul is University Senior Lecturer at the University of Cambridge Department of Pathology, and a Fellow and Director of Studies at St Catharine’s College. Rahul is a Theme Lead in Infection and Immunity at the School of Biological Sciences. Rahul studied Natural Sciences at the University of Cambridge and Clinical Medicine at King’s College London. Rahul undertook his Ph.D. at the US National Institutes of Health and a postdoctoral fellowship in Nicholas Restifo’s laboratory at the US National Cancer Institute.  Rahul was awarded a Wellcome Sir Henry Dale Fellowship in 2015 and a Lister Institute Research Prize in 2017. Rahul is a reviewer for a number of peer-reviewed scientific journals and grant agencies, and serves on the Editorial board of Immunology and the International Journal of Molecular Sciences. A major contribution of his early research was the discovery of mechanisms underlying differentiation of a powerfully suppressive subset of T cells called regulatory T (Treg) cells. His research has made fundamental contributions to our understanding of immune regulation, tumour immunosuppression and immunological memory. 

Rahul’s research group is focussed on the biology of three cell types with critical functions in inflammation, infection and tumour immunity: CD4+ regulatory T (Treg) cells, conventional CD4+ T cells and cytotoxic CD8+ T cells.

Lab website: http://roychoudhurilab.org/

 

Publications

CCR8 marks highly suppressive Treg cells within tumours but is dispensable for their accumulation and suppressive function.
Whiteside SK, Grant FM, Gyori DS, Conti AG, Imianowski CJ, Kuo P, Nasrallah R, Sadiyah F, Lira SA, Tacke F, Eil RL, Burton OT, Dooley J, Liston A, Okkenhaug K, Yang J, Roychoudhuri R
Immunology 2021 doi: 10.1111/imm.13337.

A cell-based bioluminescence assay reveals dose-dependent and contextual repression of AP-1-driven gene expression by BACH2.
Vardaka P, Lozano T, Bot C, Ellery J, Whiteside SK, Imianowski CJ, Farrow S, Walker S, Okkenhaug H, Yang J, Okkenhaug K, Kuo P, Roychoudhuri R
Sci Rep 2020 10 (1): 18902. 

BACH2 drives quiescence and maintenance of resting Treg cells to promote homeostasis and cancer immunosuppression.
Grant FM, Yang J, Nasrallah R, Clarke J, Sadiyah F, Whiteside SK, Imianowski CJ, Kuo P, Vardaka P, Todorov T, Zandhuis N, Patrascan I, Tough DF, Kometani K, Eil R, Kurosaki T, Okkenhaug K, Roychoudhuri R
J Exp Med 2020 217 (9). [PDF]
 

A distal enhancer at risk locus 11q13.5 promotes suppression of colitis by Treg cells.
Nasrallah R, Imianowski CJ, Bossini-Castillo L, Grant FM, Dogan M, Placek L, Kozhaya L, Kuo P, Sadiyah F, Whiteside SK, Mumbach MR, Glinos D, Vardaka P, Whyte CE, Lozano T, Fujita T, Fujii H, Liston A, Andrews S, Cozzani A, Yang J, Mitra S, Lugli E, Chang HY, Unutmaz D, Trynka G, Roychoudhuri R
Nature 2020 583 (7816): 447-452. [PDF]
 

IRF4 instructs effector Treg differentiation and immune suppression in human cancer.
Alvisi G, Brummelman J, Puccio S, Mazza EM, Tomada EP, 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
J Clin Invest 2020 130 (6): 3137-3150. [PDF]
 

Genome-Wide Measurement and Computational Analysis of Transcription Factor Binding and Chromatin Accessibility in Lymphocytes.
Sadiyah MF, Roychoudhuri R
Curr Protoc Immunol 2019 126 (1): e84. [PDF]
 

Regulatory T cells in cancer: where are we now?
Gallimore A, Quezada SA, Roychoudhuri R
Immunology 2019 157 (3): 187-189. [PDF]
 

Regulation of regulatory T cells in cancer.
Stockis J, Roychoudhuri R, Halim TYF
Immunology 2019 157 (3): 219-231. [PDF]
 

T cell stemness and dysfunction in tumors are triggered by a common mechanism.
Vodnala SK, Eil R, Kishton RJ, Sukumar M, Yamamoto TN, Ha NH, Lee PH, Shin M, Patel SJ, Yu Z, Palmer DC, Kruhlak MJ, Liu X, Locasale JW, Huang J, Roychoudhuri R, Finkel T, Klebanoff CA, Restifo NP
Science 2019 363 (6434). [PDF]
 

The transcription factor c-Myb regulates CD8+ T cell stemness and antitumor immunity.
Gautam S, Fioravanti J, Zhu W, Le Gall JB, Brohawn P, Lacey NE, Hu J, Hocker JD, Hawk NV, Kapoor V, Telford WG, Gurusamy D, Yu Z, Bhandoola A, Xue HH, Roychoudhuri R, Higgs BW, Restifo NP, Bender TP, Ji Y, Gattinoni L
Nat Immunol 2019 20 (3): 337-349. [PDF]
 

Paths to expansion: Differential requirements of IRF4 in CD8+ T-cell expansion driven by antigen and homeostatic cytokines.
Lugli E, Brummelman J, Pilipow K, Roychoudhuri R
Eur J Immunol 2018 48 (8): 1281-1284. [PDF]
 

Compensation between CSF1R+ macrophages and Foxp3+ Treg cells drives resistance to tumor immunotherapy.
Gyori D, Lim EL, Grant FM, Spensberger D, Roychoudhuri R, Shuttleworth SJ, Okkenhaug K, Stephens LR, Hawkins PT
JCI Insight 2018 3 (11). [PDF]
 

Phosphoinositide 3-kinase δ inhibition promotes antitumor responses but antagonizes checkpoint inhibitors.
Lim EL, Cugliandolo FM, Rosner DR, Gyori D, Roychoudhuri R, Okkenhaug K
JCI Insight 2018 3 (11). [PDF]
 

Bach2 Promotes B Cell Receptor-Induced Proliferation of B Lymphocytes and Represses Cyclin-Dependent Kinase Inhibitors.
Miura Y, Morooka M, Sax N, Roychoudhuri R, Itoh-Nakadai A, Brydun A, Funayama R, Nakayama K, Satomi S, Matsumoto M, Igarashi K, Muto A
J Immunol 2018 200 (8): 2882-2893. [PDF]
 

Epigenetic control of CD8+ T cell differentiation.
Henning AN, Roychoudhuri R, Restifo NP
Nat Rev Immunol 2018 18 (5): 340-356. [PDF]
 

BACH2 immunodeficiency illustrates an association between super-enhancers and haploinsufficiency.
Afzali B, Grönholm J, Vandrovcova J, O'Brien C, Sun HW, Vanderleyden I, Davis FP, Khoder A, Zhang Y, Hegazy AN, Villarino AV, Palmer IW, Kaufman J, Watts NR, Kazemian M, Kamenyeva O, Keith J, Sayed A, Kasperaviciute D, Mueller M, Hughes JD, Fuss IJ, Sadiyah MF, Montgomery-Recht K, McElwee J, Restifo NP, Strober W, Linterman MA, Wingfield PT, Uhlig HH, Roychoudhuri R, Aitman TJ, Kelleher P, Lenardo MJ, O'Shea JJ, Cooper N, Laurence ADJ
Nat Immunol 2017 18 (7): 813-823. [PDF]
 

BACH transcription factors in innate and adaptive immunity.
Igarashi K, Kurosaki T, Roychoudhuri R
Nat Rev Immunol 2017 17 (7): 437-450. [PDF]
 

Ionic immune suppression within the tumour microenvironment limits T cell effector function.
Eil R, Vodnala SK, Clever D, Klebanoff CA, Sukumar M, Pan JH, Palmer DC, Gros A, Yamamoto TN, Patel SJ, Guittard GC, Yu Z, Carbonaro V, Okkenhaug K, Schrump DS, Linehan WM, Roychoudhuri R, Restifo NP
Nature 2016 537 (7621): 539-543. [PDF]
 

Oxygen Sensing by T Cells Establishes an Immunologically Tolerant Metastatic Niche.
Clever D, Roychoudhuri R, Constantinides MG, Askenase MH, Sukumar M, Klebanoff CA, Eil RL, Hickman HD, Yu Z, Pan JH, Palmer DC, Phan AT, Goulding J, Gattinoni L, Goldrath AW, Belkaid Y, Restifo NP
Cell 2016 166 (5): 1117-1131.e14. [PDF]
 

Identification of novel regulators of developmental hematopoiesis using Endoglin regulatory elements as molecular probes.
Nasrallah R, Fast EM, Solaimani P, Knezevic K, Eliades A, Patel R, Thambyrajah R, Unnikrishnan A, Thoms J, Beck D, Vink CS, Smith A, Wong J, Shepherd M, Kent D, Roychoudhuri R, Paul F, Klippert J, Hammes A, Willnow T, Göttgens B, Dzierzak E, Zon LI, Lacaud G, Kouskoff V, Pimanda JE
Blood 2016 128 (15): 1928-1939. [PDF]
 

BACH2 regulates CD8(+) T cell differentiation by controlling access of AP-1 factors to enhancers.
Roychoudhuri R, Clever D, Li P, Wakabayashi Y, Quinn KM, Klebanoff CA, Ji Y, Sukumar M, Eil RL, Yu Z, Spolski R, Palmer DC, Pan JH, Patel SJ, Macallan DC, Fabozzi G, Shih HY, Kanno Y, Muto A, Zhu J, Gattinoni L, O'Shea JJ, Okkenhaug K, Igarashi K, Leonard WJ, Restifo NP
Nat Immunol 2016 17 (7): 851-860. [PDF]
 

The transcription factor BACH2 promotes tumor immunosuppression.
Roychoudhuri R, Eil RL, Clever D, Klebanoff CA, Sukumar M, Grant FM, Yu Z, Mehta G, Liu H, Jin P, Ji Y, Palmer DC, Pan JH, Chichura A, Crompton JG, Patel SJ, Stroncek D, Wang E, Marincola FM, Okkenhaug K, Gattinoni L, Restifo NP
J Clin Invest 2016 126 (2): 599-604. [PDF]
 

Mitochondrial Membrane Potential Identifies Cells with Enhanced Stemness for Cellular Therapy.
Sukumar M, Liu J, Mehta GU, Patel SJ, Roychoudhuri R, Crompton JG, Klebanoff CA, Ji Y, Li P, Yu Z, Whitehill GD, Clever D, Eil RL, Palmer DC, Mitra S, Rao M, Keyvanfar K, Schrump DS, Wang E, Marincola FM, Gattinoni L, Leonard WJ, Muranski P, Finkel T, Restifo NP
Cell Metab 2016 23 (1): 63-76. [PDF]
 

Memory T cell-driven differentiation of naive cells impairs adoptive immunotherapy.
Klebanoff CA, Scott CD, Leonardi AJ, Yamamoto TN, Cruz AC, Ouyang C, Ramaswamy M, Roychoudhuri R, Ji Y, Eil RL, Sukumar M, Crompton JG, Palmer DC, Borman ZA, Clever D, Thomas SK, Patel S, Yu Z, Muranski P, Liu H, Wang E, Marincola FM, Gros A, Gattinoni L, Rosenberg SA, Siegel RM, Restifo NP
J Clin Invest 2016 126 (1): 318-34. [PDF]
 

Oncogenic PI3Kα promotes multipotency in breast epithelial cells.
Okkenhaug K, Roychoudhuri R
Sci Signal 2015 8 (401): pe3. [PDF]
 

Cish actively silences TCR signaling in CD8+ T cells to maintain tumor tolerance.
Palmer DC, Guittard GC, Franco Z, Crompton JG, Eil RL, Patel SJ, Ji Y, Van Panhuys N, Klebanoff CA, Sukumar M, Clever D, Chichura A, Roychoudhuri R, Varma R, Wang E, Gattinoni L, Marincola FM, Balagopalan L, Samelson LE, Restifo NP
J Exp Med 2015 212 (12): 2095-113. [PDF]
 

Transcriptional repressor ZEB2 promotes terminal differentiation of CD8+ effector and memory T cell populations during infection.
Omilusik KD, Best JA, Yu B, Goossens S, Weidemann A, Nguyen JV, Seuntjens E, Stryjewska A, Zweier C, Roychoudhuri R, Gattinoni L, Bird LM, Higashi Y, Kondoh H, Huylebroeck D, Haigh J, Goldrath AW
J Exp Med 2015 212 (12): 2027-39. [PDF]
 

Nutrient Competition: A New Axis of Tumor Immunosuppression.
Sukumar M, Roychoudhuri R, Restifo NP
Cell 2015 162 (6): 1206-8. [PDF]
 

The kinase DYRK1A reciprocally regulates the differentiation of Th17 and regulatory T cells.
Khor B, Gagnon JD, Goel G, Roche MI, Conway KL, Tran K, Aldrich LN, Sundberg TB, Paterson AM, Mordecai S, Dombkowski D, Schirmer M, Tan PH, Bhan AK, Roychoudhuri R, Restifo NP, O'Shea JJ, Medoff BD, Shamji AF, Schreiber SL, Sharpe AH, Shaw SY, Xavier RJ
Elife 2015 4 (). [PDF]
 

Lineage relationship of CD8(+) T cell subsets is revealed by progressive changes in the epigenetic landscape.
Crompton JG, Narayanan M, Cuddapah S, Roychoudhuri R, Ji Y, Yang W, Patel SJ, Sukumar M, Palmer DC, Peng W, Wang E, Marincola FM, Klebanoff CA, Zhao K, Tsang JS, Gattinoni L, Restifo NP
Cell Mol Immunol 2016 13 (4): 502-13. [PDF]
 

The interplay of effector and regulatory T cells in cancer.
Roychoudhuri R, Eil RL, Restifo NP
Curr Opin Immunol 2015 33 (): 101-11. [PDF]
 

Super-enhancers delineate disease-associated regulatory nodes in T cells.
Vahedi G, Kanno Y, Furumoto Y, Jiang K, Parker SC, Erdos MR, Davis SR, Roychoudhuri R, Restifo NP, Gadina M, Tang Z, Ruan Y, Collins FS, Sartorelli V, O'Shea JJ
Nature 2015 520 (7548): 558-62. [PDF]
 

miR-155 augments CD8+ T-cell antitumor activity in lymphoreplete hosts by enhancing responsiveness to homeostatic γc cytokines.
Ji Y, Wrzesinski C, Yu Z, Hu J, Gautam S, Hawk NV, Telford WG, Palmer DC, Franco Z, Sukumar M, Roychoudhuri R, Clever D, Klebanoff CA, Surh CD, Waldmann TA, Restifo NP, Gattinoni L
Proc Natl Acad Sci U S A 2015 112 (2): 476-81. [PDF]
 

Transcriptional profiles reveal a stepwise developmental program of memory CD8(+) T cell differentiation.
Roychoudhuri R, Lefebvre F, Honda M, Pan L, Ji Y, Klebanoff CA, Nichols CN, Fourati S, Hegazy AN, Goulet JP, Gattinoni L, Nabel GJ, Gilliet M, Cameron M, Restifo NP, Sékaly RP, Flatz L
Vaccine 2015 33 (7): 914-23. [PDF]
 

Akt inhibition enhances expansion of potent tumor-specific lymphocytes with memory cell characteristics.
Crompton JG, Sukumar M, Roychoudhuri R, Clever D, Gros A, Eil RL, Tran E, Hanada K, Yu Z, Palmer DC, Kerkar SP, Michalek RD, Upham T, Leonardi A, Acquavella N, Wang E, Marincola FM, Gattinoni L, Muranski P, Sundrud MS, Klebanoff CA, Rosenberg SA, Fearon DT, Restifo NP
Cancer Res 2015 75 (2): 296-305. [PDF]
 

Type I cytokines synergize with oncogene inhibition to induce tumor growth arrest.
Acquavella N, Clever D, Yu Z, Roelke-Parker M, Palmer DC, Xi L, Pflicke H, Ji Y, Gros A, Hanada K, Goldlust IS, Mehta GU, Klebanoff CA, Crompton JG, Sukumar M, Morrow JJ, Franco Z, Gattinoni L, Liu H, Wang E, Marincola F, Stroncek DF, Lee CC, Raffeld M, Bosenberg MW, Roychoudhuri R, Restifo NP
Cancer Immunol Res 2015 3 (1): 37-47. [PDF]
 

Identification of the genomic insertion site of Pmel-1 TCR α and β transgenes by next-generation sequencing.
Ji Y, Abrams N, Zhu W, Salinas E, Yu Z, Palmer DC, Jailwala P, Franco Z, Roychoudhuri R, Stahlberg E, Gattinoni L, Restifo NP
PLoS One 2014 9 (5): e96650. 
 

Inhibiting glycolytic metabolism enhances CD8+ T cell memory and antitumor function.
Sukumar M, Liu J, Ji Y, Subramanian M, Crompton JG, Yu Z, Roychoudhuri R, Palmer DC, Muranski P, Karoly ED, Mohney RP, Klebanoff CA, Lal A, Finkel T, Restifo NP, Gattinoni L
J Clin Invest 2013 123 (10): 4479-88. [PDF]
 

Retinoic acid controls the homeostasis of pre-cDC-derived splenic and intestinal dendritic cells.
Klebanoff CA, Spencer SP, Torabi-Parizi P, Grainger JR, Roychoudhuri R, Ji Y, Sukumar M, Muranski P, Scott CD, Hall JA, Ferreyra GA, Leonardi AJ, Borman ZA, Wang J, Palmer DC, Wilhelm C, Cai R, Sun J, Napoli JL, Danner RL, Gattinoni L, Belkaid Y, Restifo NP
J Exp Med 2013 210 (10): 1961-76. [PDF]
 

BACH2 represses effector programs to stabilize T(reg)-mediated immune homeostasis.
Roychoudhuri R, Hirahara K, Mousavi K, Clever D, Klebanoff CA, Bonelli M, Sciumè G, Zare H, Vahedi G, Dema B, Yu Z, Liu H, Takahashi H, Rao M, Muranski P, Crompton JG, Punkosdy G, Bedognetti D, Wang E, Hoffmann V, Rivera J, Marincola FM, Nakamura A, Sartorelli V, Kanno Y, Gattinoni L, Muto A, Igarashi K, O'Shea JJ, Restifo NP
Nature 2013 498 (7455): 506-10. [PDF]
 

Gene-based vaccination with a mismatched envelope protects against simian immunodeficiency virus infection in nonhuman primates.
Flatz L, Cheng C, Wang L, Foulds KE, Ko SY, Kong WP, Roychoudhuri R, Shi W, Bao S, Todd JP, Asmal M, Shen L, Donaldson M, Schmidt SD, Gall JG, Pinschewer DD, Letvin NL, Rao S, Mascola JR, Roederer M, Nabel GJ
J Virol 2012 86 (15): 7760-70. [PDF]
 

Th17 cells are long lived and retain a stem cell-like molecular signature.
Muranski P, Borman ZA, Kerkar SP, Klebanoff CA, Ji Y, Sanchez-Perez L, Sukumar M, Reger RN, Yu Z, Kern SJ, Roychoudhuri R, Ferreyra GA, Shen W, Durum SK, Feigenbaum L, Palmer DC, Antony PA, Chan CC, Laurence A, Danner RL, Gattinoni L, Restifo NP
Immunity 2011 35 (6): 972-85. [PDF]
 

Permissivity of the NCI-60 cancer cell lines to oncolytic Vaccinia Virus GLV-1h68.
Ascierto ML, Worschech A, Yu Z, Adams S, Reinboth J, Chen NG, Pos Z, Roychoudhuri R, Di Pasquale G, Bedognetti D, Uccellini L, Rossano F, Ascierto PA, Stroncek DF, Restifo NP, Wang E, Szalay AA, Marincola FM
BMC Cancer 2011 11 (): 451. [PDF]
 

Single-cell gene-expression profiling reveals qualitatively distinct CD8 T cells elicited by different gene-based vaccines.
Flatz L, Roychoudhuri R, Honda M, Filali-Mouhim A, Goulet JP, Kettaf N, Lin M, Roederer M, Haddad EK, Sékaly RP, Nabel GJ
Proc Natl Acad Sci U S A 2011 108 (14): 5724-9. [PDF]
 

Season of cancer diagnosis exerts distinct effects upon short- and long-term survival.
Roychoudhuri R, Robinson D, Coupland V, Holmberg L, Møller H
Int J Cancer 2009 124 (10): 2436-41. [PDF]
 

Increased cardiovascular mortality more than fifteen years after radiotherapy for breast cancer: a population-based study.
Roychoudhuri R, Robinson D, Putcha V, Cuzick J, Darby S, Møller H
BMC Cancer 2007 7 (): 9. [PDF]
 

Cancer survival is dependent on season of diagnosis and sunlight exposure.
Lim HS, Roychoudhuri R, Peto J, Schwartz G, Baade P, Møller H
Int J Cancer 2006 119 (7): 1530-6. [PDF]
 

Cancer and laterality: a study of the five major paired organs (UK).
Roychoudhuri R, Putcha V, Møller H
Cancer Causes Control 2006 17 (5): 655-62. [PDF]
 

Radiation-induced malignancies following radiotherapy for breast cancer.
Roychoudhuri R, Evans H, Robinson D, Møller H
Br J Cancer 2004 91 (5): 868-72. [PDF]

University Senior Lecturer, Division of Immunology
Theme Lead in Infection and Immunity
Director of Studies in Pathology, St Catharine's College
Dr Rahul  Roychoudhuri

Contact Details

Takes PhD students
Not available for consultancy

Affiliations

Specialities: 
Departments and institutes: 
Person keywords: 
Immunology
Inflammation
Cancer
Biology
Immune regulation