M. Ayyoub

  T2i : Tumor immunity and immunotherapy







Our research project at a glance


Decades-long efforts in tumor immunology research have recently come to fruition with the clinical success of monoclonal antibodies targeting immune checkpoints. These therapies have allowed, on one hand, to confirm the central role of adaptive immunity in the control of tumor growth and, on the other, to underline the importance of immune regulatory mechanisms in the ability of tumors to escape immune control. The aim of our research is to decipher the molecular and cellular mechanisms underlying tumors sensitivity/resistance to immunotherapy in order to design combination therapies able to prevail over resistance.



Despite its efficacy across several malignancies, only a proportion of treated patients experience clinical benefit from immune checkpoint modulation monotherapy. In addition, a number of tumor types, while being immunogenic, do not respond to current immunotherapies.

In order to understand the molecular and cellular mechanisms of tumors sensitivity/resistance to spontaneous or therapeutic immune responses, our studies are focused on:

  • deciphering the impact of tumor antigen-specific adaptive responses to tumor immune sensitivity through the assessment of T cell responses to neoantigens, oncoviral antigens and cancer testis antigens, of the mechanisms underlying the immunogenicity of these antigen categories and of the evolution of tumor-specific T cell responses along immune checkpoint modulation therapy;
  • investigating the contribution of the T cell response type (type 1/Th1/Tc1; type 2/th2; type 3/Th17; Treg) to anti-tumor immunity according to tumor histological type and anatomic location.

The results of our studies have potential impact on the identification of clinically meaningful biomarkers of response to immunotherapy and on the development of combination therapies, in particular cancer vaccines associated to immune checkpoint modulation, which can enhance the extent of clinical responses to immunotherapy.


Key words

  • Antitumor T cell response
  • CD4 T cell populations
  • Immune checkpoint modulators
  • Anticancer vaccines


Labels and networks


Selected publications


Zitvogel, L; Ayyoub, M; Routy, B; Kroemer, G

Microbiome and Anticancer Immunosurveillance Journal Article

Cell, 165 (2), pp. 276-87, 2016, ISSN: 1097-4172 (Electronic) 0092-8674 (Linking).

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Scarlata, C M; Celse, C; Pignon, P; Ayyoub, M; Valmori, D

Differential expression of the immunosuppressive enzyme IL4I1 in human induced Aiolos+, but not natural Helios+, FOXP3+ Treg cells Journal Article

Eur J Immunol, 45 (2), pp. 474-9, 2015, ISSN: 1521-4141 (Electronic) 0014-2980 (Linking).

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Ayyoub, M; Pignon, P; Classe, J M; Odunsi, K; Valmori, D

CD4+ T effectors specific for the tumor antigen NY-ESO-1 are highly enriched at ovarian cancer sites and coexist with, but are distinct from, tumor-associated Treg Journal Article

Cancer Immunol Res, 1 (5), pp. 303-8, 2013, ISSN: 2326-6074 (Electronic) 2326-6066 (Linking).

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Hamai, A; Pignon, P; Raimbaud, I; Duperrier-Amouriaux, K; Senellart, H; Hiret, S; Douillard, J Y; Bennouna, J; Ayyoub, M; Valmori, D

Human T(H)17 immune cells specific for the tumor antigen MAGE-A3 convert to IFN-gamma-secreting cells as they differentiate into effector T cells in vivo Journal Article

Cancer Res, 72 (5), pp. 1059-63, 2012, ISSN: 1538-7445 (Electronic) 0008-5472 (Linking).

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Redjimi, N; Raffin, C; Raimbaud, I; Pignon, P; Matsuzaki, J; Odunsi, K; Valmori, D; Ayyoub, M

CXCR3+ T regulatory cells selectively accumulate in human ovarian carcinomas to limit type I immunity Journal Article

Cancer Res, 72 (17), pp. 4351-60, 2012, ISSN: 1538-7445 (Electronic) 0008-5472 (Linking).

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Valmori, D; Raffin, C; Raimbaud, I; Ayyoub, M

Human RORgammat+ TH17 cells preferentially differentiate from naive FOXP3+Treg in the presence of lineage-specific polarizing factors Journal Article

Proc Natl Acad Sci U S A, 107 (45), pp. 19402-7, 2010, ISSN: 1091-6490 (Electronic) 0027-8424 (Linking).

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Bioley, G; Guillaume, P; Luescher, I; Yeh, A; Dupont, B; Bhardwaj, N; Mears, G; Old, L J; Valmori, D; Ayyoub, M

HLA class I - associated immunodominance affects CTL responsiveness to an ESO recombinant protein tumor antigen vaccine Journal Article

Clin Cancer Res, 15 (1), pp. 299-306, 2009, ISSN: 1078-0432 (Print) 1078-0432 (Linking).

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Valmori, D; Merlo, A; Souleimanian, N E; Hesdorffer, C S; Ayyoub, M

A peripheral circulating compartment of natural naive CD4 Tregs Journal Article

J Clin Invest, 115 (7), pp. 1953-62, 2005, ISSN: 0021-9738 (Print) 0021-9738 (Linking).

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