Amira Ben Amara

Centre de Recherche en Cancérologie de Marseille

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Laurent Gorvel

Inserm

Daniel Olive

Centre de Recherche en Cancérologie de Marseille

Anne-Sophie Chrétien

Centre de Recherche en Cancérologie de Marseille

Nicolas Boucherit

Centre de Recherche en Cancérologie de Marseille

Samuel Granjeaud

Centre de Recherche en Cancérologie de Marseille

Stéphane Fattori

Centre de Recherche en Cancérologie de Marseille

ÉL

Éric Lambaudie

Institut Paoli-Calmettes

Marie-Sarah Rouvière

Centre de Recherche en Cancérologie de Marseille

Aude Le Roy

Centre de Recherche en Cancérologie de Marseille

Jihane Pakradouni

Institut Paoli-Calmettes

Cooperative Institutions

Inserm

148

Centre National de la Recherche Scientifique

128

Aix-Marseille Université

125

Institut Paoli-Calmettes

Centre de Recherche en Cancérologie de Marseille

South China Agricultural University

University of Westminster

Fundação Oswaldo Cruz

Institut de Recherche pour le Développement

University of California, Davis

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Supplementary_Materials_and_Methods_Figures_and_Figure_legends from CD25high Effector Regulatory T Cells Hamper Responses to PD-1 Blockade in Triple-Negative Breast Cancer

Stéphane Fattori Aude Le Roy Jemila Houacine Lucie Robert Riad Abès

Supplementary_Materials_and_Methods_Figures_and_Figure_legends

10.1158/0008-5472.24146019.v1

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Table S2 from CD25high Effector Regulatory T Cells Hamper Responses to PD-1 Blockade in Triple-Negative Breast Cancer

Stéphane Fattori Aude Le Roy Jemila Houacine Lucie Robert Riad Abès

T cell and NK cell subpopulations gene features, related to Figure 1

Triple-negative breast cancer

10.1158/0008-5472.24146013

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Table S6 from CD25high Effector Regulatory T Cells Hamper Responses to PD-1 Blockade in Triple-Negative Breast Cancer

Stéphane Fattori Aude Le Roy Jemila Houacine Lucie Robert Riad Abès

Mass cytometry panels, related to Figure 1

Triple-negative breast cancer

10.1158/0008-5472.24145998.v1

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Intracellular Bacteria Interfere with Dendritic Cell Functions: Role of the Type I Interferon Pathway

PLoS ONE (2014)

Laurent Gorvel Julien Textoris Romain Banchereau Amira Ben Amara Wiwit Tantibhedhyangkul

Dendritic cells (DCs) orchestrate host defenses against microorganisms. In infectious diseases due to intracellular bacteria, the inefficiency of the immune system to eradicate microorganisms has been attributed to the hijacking of DC functions. In this study, we selected intracellular bacterial pathogens with distinct lifestyles and explored the responses of monocyte-derived DCs (moDCs). Using lipopolysaccharide as a control, we found that Orientia tsutsugamushi, the causative agent of scrub typhus that survives in the cytosol of target cells, induced moDC maturation, as assessed by decreased endocytosis activity, the ability to induce lymphocyte proliferation and the membrane expression of phenotypic markers. In contrast, Coxiella burnetii, the agent of Q fever, and Brucella abortus, the agent of brucellosis, both of which reside in vacuolar compartments, only partly induced the maturation of moDCs, as demonstrated by a phenotypic analysis. To analyze the mechanisms used by C. burnetii and B. abortus to alter moDC activation, we performed microarray and found that C. burnetii and B. abortus induced a specific signature consisting of TLR4, TLR3, STAT1 and interferon response genes. These genes were down-modulated in response to C. burnetii and B. abortus but up-modulated in moDCs activated by lipopolysaccharide and O. tsutsugamushi. This transcriptional alteration was associated with the defective interferon-β production. This study demonstrates that intracellular bacteria specifically affect moDC responses and emphasizes how C. burnetii and B. abortus interfere with moDC activation and the antimicrobial immune response. We believe that comparing infection by several bacterial species may be useful for defining new pathways and biomarkers and for developing new treatment strategies.

Coxiella burnetii

Intracellular parasite

10.1371/journal.pone.0099420

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Citations (46)

Table S1 from CD25high Effector Regulatory T Cells Hamper Responses to PD-1 Blockade in Triple-Negative Breast Cancer

Stéphane Fattori Aude Le Roy Jemila Houacine Lucie Robert Riad Abès

Clinical characteristics of patients with breast cancer

Table (database)

10.1158/0008-5472.27028507

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Table S3 from CD25high Effector Regulatory T Cells Hamper Responses to PD-1 Blockade in Triple-Negative Breast Cancer

Stéphane Fattori Aude Le Roy Jemila Houacine Lucie Robert Riad Abès

cDC_monocyte_macrophage subpopulations gene features, related to Figure 1

Triple-negative breast cancer

Table (database)

10.1158/0008-5472.27028501

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Persistence of Coxiella burnetii, the Agent of Q Fever, in Murine Adipose Tissue

PLoS ONE (2014)

Yassina Bechah Johanna Verneau Amira Ben Amara Abdoulaye Barry Catherine Lépolard

Coxiella burnetii, the agent of Q fever, is known to persist in humans and rodents but its cellular reservoir in hosts remains undetermined. We hypothesized that adipose tissue serves as a C. burnetii reservoir during bacterial latency. BALB/c and C57BL/6 mice were infected with C. burnetii by the intraperitoneal route or the intracheal route. Adipose tissue was tested for the presence of C. burnetii several months after infection. C. burnetii was detected in abdominal, inguinal and dorsal adipose tissue 4 months post-infection, when no bacteria were detected in blood, liver, lungs and spleen, regardless of the inoculation route and independently of mouse strain. The transfer of abdominal adipose tissue from convalescent BALB/c mice to naïve immunodeficient mice resulted in the infection of the recipient animals. It is likely that C. burnetii infects adipocytes in vivo because bacteria were found in adipocytes within adipose tissue and replicated within in vitro-differentiated adipocytes. In addition, C. burnetii induced a specific transcriptional program in in-vivo and in vitro-differentiated adipocytes, which was enriched in categories associated with inflammatory response, hormone response and cytoskeleton. These changes may account for bacterial replication in in-vitro and chronic infection in-vivo. Adipose tissue may be the reservoir in which C. burnetii persists for prolonged periods after apparent clinical cure. The mouse model of C. burnetii infection may be used to understand the relapses of Q fever and provide new perspectives to the follow-up of patients.

Coxiella burnetii

Q fever

10.1371/journal.pone.0097503

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Citations (41)

Randomized Phase 2 Trial of Lirilumab as maintenance Treatment in Acute Myeloid Leukemia: Results of the EFFIKIR Trial

medRxiv (Cold Spring Harbor Laboratory) (2024)

Norbert Vey Anne-Sophie Chrétien P Dumas Christian Récher Lauris Gastaud

ABSTRACT Lirilumab is a fully human monoclonal antibody designed to block killer inhibitory receptors (KIR), which are major immune checkpoints involved in the regulation of NK cell-mediated killing of HLA-I-expressing tumors. EFFIKIR is a multicenter randomized double-blind 3-arm placebo-controlled phase II trial with lirilumab as single-agent as maintenance therapy of elderly patients with AML in first complete remission ( NCT01687387 ). Two dose schedules led to either continuous or intermittent KIR occupancy. 153 patients were randomized and 152 patients were treated after 3+7 induction therapy. The median follow-up was 36.6 months. Lirilumab was well tolerated, with no significant hematological toxicity. The median LFS were 17.6, 6.7 and 13.9 months in the 0.1mg/kg arm, 1mg/kg arm and placebo arm, respectively. An excess in early relapse led to early termination of treatment in the 1mg/kg arm. Extensive analysis of immune cell fate following KIR blockade evidenced a decrease of KIR + NK cell absolute counts following KIR blockade, associated with a decrease of Bcl-2. Lirilumab also bound antigen-experienced CD8 + T cells, and induced a transient decrease of CD69 expression. Besides, lirilumab bound vδ2 + γδT cells with a high cytotoxic potential, and induced a decrease of DNAM-1 and Bcl-2, the latter being associated with a decrease of KIR + γδT cell, and with a drastic reduction of time to relapse. Overall, the potentially deleterious effects on immune effectors may have resulted in the impairment of immune surveillance associated with an unexpected high rate of early relapse in the group of patients exposed to prolonged full KIR blockade. KEY POINTS Prolonged full KIR blockade leads to potentially deleterious effects on NK cells, CD8 + T cells and vδ2 + γδT cells Combined inhibitory effects of KIR blockade may have resulted in the impairment of immunosurveillance associated with high rate of relapse

10.1101/2024.08.23.24312477

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Intact interferon-γ response against Coxiella burnetii by peripheral blood mononuclear cells in chronic Q fever

Clinical Microbiology and Infection (2016)

Teske Schoffelen Julien Textoris Chantal P. Bleeker‐Rovers Amira Ben Amara J.W.M. van der Meer

Coxiella burnetii

Q fever

Neopterin

10.1016/j.cmi.2016.11.008

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Citations (21)