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Article ; Online: Activated B-Cells enhance epitope spreading to support successful cancer immunotherapy.

Kellermann, Guillaume / Leulliot, Nicolas / Cherfils-Vicini, Julien / Blaud, Magali / Brest, Patrick

2024 Volume 15, Page(s) 1382236

Abstract: Immune checkpoint therapies (ICT) have transformed the treatment of cancer over the past decade. However, many patients do not respond or suffer relapses. Successful immunotherapy requires epitope spreading, but the slow or inefficient induction of ... ...

Abstract	Immune checkpoint therapies (ICT) have transformed the treatment of cancer over the past decade. However, many patients do not respond or suffer relapses. Successful immunotherapy requires epitope spreading, but the slow or inefficient induction of functional antitumoral immunity delays the benefit to patients or causes resistances. Therefore, understanding the key mechanisms that support epitope spreading is essential to improve immunotherapy. In this review, we highlight the major role played by B-cells in breaking immune tolerance by epitope spreading. Activated B-cells are key Antigen-Presenting Cells (APC) that diversify the T-cell response against self-antigens, such as ribonucleoproteins, in autoimmunity but also during successful cancer immunotherapy. This has important implications for the design of future cancer vaccines.
MeSH term(s)	Humans ; Epitopes ; T-Lymphocytes ; Autoantigens ; Autoimmunity ; Immunotherapy ; Neoplasms/therapy
Chemical Substances	Epitopes ; Autoantigens
Language	English
Publishing date	2024-03-19
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2024.1382236
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Checkpoint inhibitors and anti-angiogenic agents: a winning combination.

Brest, Patrick / Mograbi, Baharia / Pagès, Gilles / Hofman, Paul / Milano, Gerard

British journal of cancer

2023 Volume 129, Issue 9, Page(s) 1367–1372

Abstract: The combination of immune checkpoint inhibitors and anti-angiogenic agents is a promising new approach in cancer treatment. Immune checkpoint inhibitors block the signals that help cancer cells evade the immune system, while anti-angiogenic agents target ...

Abstract	The combination of immune checkpoint inhibitors and anti-angiogenic agents is a promising new approach in cancer treatment. Immune checkpoint inhibitors block the signals that help cancer cells evade the immune system, while anti-angiogenic agents target the blood vessels that supply the tumour with nutrients and oxygen, limiting its growth. Importantly, this combination triggers synergistic effects based on molecular and cellular mechanisms, leading to better response rates and longer progression-free survival than treatment alone. However, these combinations can also lead to increased side effects and require close monitoring.
MeSH term(s)	Humans ; Immune Checkpoint Inhibitors/therapeutic use ; Neovascularization, Pathologic/drug therapy ; Angiogenesis Inhibitors/pharmacology ; Neoplasms/drug therapy
Chemical Substances	Immune Checkpoint Inhibitors ; Angiogenesis Inhibitors
Language	English
Publishing date	2023-09-21
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	80075-2
ISSN	1532-1827 ; 0007-0920
ISSN (online)	1532-1827
ISSN	0007-0920
DOI	10.1038/s41416-023-02437-1
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Article: Host genetic variability and determinants of severe COVID-19.

Brest, Patrick / Mograbi, Baharia / Gal, Jocelyn / Hofman, Paul / Milano, Gerard

Trends in genetics : TIG

2022 Volume 39, Issue 3, Page(s) 169–171

Abstract: Since the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak, convergent studies have provided evidence that host genetic background may contribute to the development of severe coronavirus disease (COVID-19). Here, we summarize how ... ...

Abstract	Since the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak, convergent studies have provided evidence that host genetic background may contribute to the development of severe coronavirus disease (COVID-19). Here, we summarize how some genetic variations, such as in SARS-CoV-2 receptor angiotensin-converting enzyme 2 or interferon signaling pathway, may help to understand why some individuals can develop severe COVID-19.
MeSH term(s)	Humans ; SARS-CoV-2/metabolism ; COVID-19 ; Peptidyl-Dipeptidase A/genetics
Chemical Substances	Peptidyl-Dipeptidase A (EC 3.4.15.1)
Language	English
Publishing date	2022-11-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	619240-3
ISSN	1362-4555 ; 0168-9525 ; 0168-9479
ISSN (online)	1362-4555
ISSN	0168-9525 ; 0168-9479
DOI	10.1016/j.tig.2022.10.003
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Article ; Online: More light on cancer and COVID-19 reciprocal interaction.

Brest, Patrick / Mograbi, Baharia / Hofman, Paul / Milano, Gerard

British journal of cancer

2021 Volume 124, Issue 8, Page(s) 1344–1345

Abstract: Cancer patients are vulnerable to COVID-19 with consequences on treatment delays and on mortality rate. This Comment explores the interaction between COVID-19 and cancer with attention paid to the modulation by cancer treatments of both ADAM17 and ... ...

Abstract	Cancer patients are vulnerable to COVID-19 with consequences on treatment delays and on mortality rate. This Comment explores the interaction between COVID-19 and cancer with attention paid to the modulation by cancer treatments of both ADAM17 and TMPRSS2, the proteases which control ACE2 processing, the SARS-CoV-2 target.
MeSH term(s)	ADAM17 Protein/genetics ; Angiotensin-Converting Enzyme 2/genetics ; COVID-19/complications ; COVID-19/epidemiology ; COVID-19/genetics ; COVID-19/virology ; Humans ; Mortality ; Neoplasms/complications ; Neoplasms/epidemiology ; Neoplasms/genetics ; Neoplasms/virology ; SARS-CoV-2/genetics ; SARS-CoV-2/pathogenicity ; Serine Endopeptidases/genetics
Chemical Substances	Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Serine Endopeptidases (EC 3.4.21.-) ; TMPRSS2 protein, human (EC 3.4.21.-) ; ADAM17 Protein (EC 3.4.24.86) ; ADAM17 protein, human (EC 3.4.24.86)
Language	English
Publishing date	2021-02-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80075-2
ISSN	1532-1827 ; 0007-0920
ISSN (online)	1532-1827
ISSN	0007-0920
DOI	10.1038/s41416-020-01246-0
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Article ; Online: COVID-19 vaccination and cancer immunotherapy: should they stick together?

Brest, Patrick / Mograbi, Baharia / Hofman, Paul / Milano, Gerard

British journal of cancer

2021 Volume 126, Issue 1, Page(s) 1–3

Abstract: The combination of COVID-19 vaccination with immunotherapy by checkpoint inhibitors in cancer patients could intensify immunological stimulation with potential reciprocal benefits. Here, we examine more closely the possible adverse events that can arise ... ...

Abstract	The combination of COVID-19 vaccination with immunotherapy by checkpoint inhibitors in cancer patients could intensify immunological stimulation with potential reciprocal benefits. Here, we examine more closely the possible adverse events that can arise in each treatment modality. Our conclusion is that caution should be exercised when combining both treatments.
MeSH term(s)	BNT162 Vaccine/administration & dosage ; BNT162 Vaccine/adverse effects ; BNT162 Vaccine/immunology ; COVID-19/immunology ; COVID-19/prevention & control ; COVID-19 Vaccines/administration & dosage ; COVID-19 Vaccines/adverse effects ; COVID-19 Vaccines/immunology ; Combined Modality Therapy/adverse effects ; Cytokine Release Syndrome/etiology ; Drug Interactions ; Humans ; Immune Checkpoint Inhibitors/administration & dosage ; Immune Checkpoint Inhibitors/adverse effects ; Immunotherapy/adverse effects ; Immunotherapy/methods ; Neoplasms/immunology ; Neoplasms/therapy
Chemical Substances	COVID-19 Vaccines ; Immune Checkpoint Inhibitors ; BNT162 Vaccine (N38TVC63NU)
Language	English
Publishing date	2021-11-19
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80075-2
ISSN	1532-1827 ; 0007-0920
ISSN (online)	1532-1827
ISSN	0007-0920
DOI	10.1038/s41416-021-01618-0
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Article: Daily Practice Assessment of

Bontoux, Christophe / Hofman, Véronique / Brest, Patrick / Ilié, Marius / Mograbi, Baharia / Hofman, Paul

Cancers

2022 Volume 14, Issue 7

Abstract: ... ...

Abstract	KRAS
Language	English
Publishing date	2022-03-23
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14071628
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Article: Using Genetics To Dissect SARS-CoV-2 Infection.

Brest, Patrick / Mograbi, Baharia / Hofman, Paul / Milano, Gerard

Trends in genetics : TIG

2020 Volume 37, Issue 3, Page(s) 203–204

Abstract: To uncover the key cellular pathways associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectivity, Daniloski and coworkers used CRISPR-based whole-genome screening. Their results could propose new or repositioned drugs for the ...

Abstract	To uncover the key cellular pathways associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectivity, Daniloski and coworkers used CRISPR-based whole-genome screening. Their results could propose new or repositioned drugs for the ongoing fight against COVID-19.
MeSH term(s)	Angiotensin-Converting Enzyme 2/genetics ; Angiotensin-Converting Enzyme 2/metabolism ; COVID-19/genetics ; COVID-19/metabolism ; COVID-19/virology ; CRISPR-Cas Systems ; Gene Editing/methods ; Gene Expression ; Genome, Viral/genetics ; Genome-Wide Association Study/methods ; Humans ; RNA Interference ; SARS-CoV-2/genetics ; SARS-CoV-2/metabolism ; SARS-CoV-2/physiology
Chemical Substances	ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
Language	English
Publishing date	2020-11-26
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	619240-3
ISSN	1362-4555 ; 0168-9525 ; 0168-9479
ISSN (online)	1362-4555
ISSN	0168-9525 ; 0168-9479
DOI	10.1016/j.tig.2020.11.007
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Article ; Online: PD-L1 regulation revisited: impact on immunotherapeutic strategies.

Lucibello, Giulia / Mograbi, Baharia / Milano, Gerard / Hofman, Paul / Brest, Patrick

Trends in molecular medicine

2021 Volume 27, Issue 9, Page(s) 868–881

Abstract: A particularly promising cancer treatment is the use of monoclonal antibodies (mAbs) against immune checkpoints (i.e., immune checkpoint inhibitors; ICIs). However, many patients experience relapse and severe adverse events. To overcome these negative ... ...

Abstract	A particularly promising cancer treatment is the use of monoclonal antibodies (mAbs) against immune checkpoints (i.e., immune checkpoint inhibitors; ICIs). However, many patients experience relapse and severe adverse events. To overcome these negative issues and improve efficiency, current approaches rely on combinatorial treatments, including some modulating the expression of programmed cell death receptor 1 (PD-1)/programmed death ligand 1 (PD-L1) immune checkpoints directly. In this review, we examine the recently discovered pathways involved in PD-L1 expression and highlight the relevant druggable strategies that are being developed to both improve the response rate and avoid the onset of resistance. Altogether, these new strategies will pave the way for effective treatment combinations in future oncology clinical trials.
MeSH term(s)	Antibodies, Monoclonal/therapeutic use ; B7-H1 Antigen ; Humans ; Immunotherapy ; Neoplasms/therapy ; Programmed Cell Death 1 Receptor
Chemical Substances	Antibodies, Monoclonal ; B7-H1 Antigen ; Programmed Cell Death 1 Receptor
Language	English
Publishing date	2021-06-26
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2036490-8
ISSN	1471-499X ; 1471-4914
ISSN (online)	1471-499X
ISSN	1471-4914
DOI	10.1016/j.molmed.2021.06.005
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Article ; Online: Manipulating the gut and tumor microbiota for immune checkpoint inhibitor therapy: from dream to reality.

Guillot, Nicolas / Roméo, Barnabé / Manesh, Shima Sepehri / Milano, Gerard / Brest, Patrick / Zitvogel, Laurence / Hofman, Paul / Mograbi, Baharia

Trends in molecular medicine

2023 Volume 29, Issue 11, Page(s) 897–911

Abstract: The past decade has witnessed a revolution in cancer treatment by shifting from conventional therapies to immune checkpoint inhibitors (ICIs). These immunotherapies unleash the host immune system against the tumor and have achieved unprecedented durable ... ...

Abstract	The past decade has witnessed a revolution in cancer treatment by shifting from conventional therapies to immune checkpoint inhibitors (ICIs). These immunotherapies unleash the host immune system against the tumor and have achieved unprecedented durable remission. However, 80% of patients do not respond. This review discusses how bacteria are unexpected drivers that reprogram tumor immunity. Manipulating the microbiota impacts on tumor development and reprograms the tumor microenvironment (TME) of mice on immunotherapy. We anticipate that harnessing commensals and the tumor microbiome holds promise to identify patients who will benefit from immunotherapy and guide the choice of new ICI combinations to advance treatment efficacy.
MeSH term(s)	Humans ; Animals ; Mice ; Immune Checkpoint Inhibitors/pharmacology ; Immune Checkpoint Inhibitors/therapeutic use ; Immunotherapy ; Neoplasms/drug therapy ; Neoplasms/etiology ; Microbiota ; Tumor Microenvironment
Chemical Substances	Immune Checkpoint Inhibitors
Language	English
Publishing date	2023-09-11
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2036490-8
ISSN	1471-499X ; 1471-4914
ISSN (online)	1471-499X
ISSN	1471-4914
DOI	10.1016/j.molmed.2023.08.004
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Article ; Online: Should evidence of an autolysosomal de-acidification defect in Alzheimer and Parkinson diseases call for caution in prescribing chronic PPI and DMARD?

Giuliano, Sandy / Montemagno, Christopher / Domdom, Marie-Angela / Teisseire, Manon / Brest, Patrick / Klionsky, Daniel J / Hofman, Paul / Pagès, Gilles / Mograbi, Baharia

Autophagy

2023 Volume 19, Issue 10, Page(s) 2800–2806

Abstract: Nearly fifty million older people suffer from neurodegenerative diseases, including Alzheimer (AD) and Parkinson (PD) disease, a global burden expected to triple by 2050. Such an imminent "neurological pandemic" urges the identification of environmental ... ...

Abstract	Nearly fifty million older people suffer from neurodegenerative diseases, including Alzheimer (AD) and Parkinson (PD) disease, a global burden expected to triple by 2050. Such an imminent "neurological pandemic" urges the identification of environmental risk factors that are hopefully avoided to fight the disease. In 2022, strong evidence in mouse models incriminated defective lysosomal acidification and impairment of the autophagy pathway as modifiable risk factors for dementia. To date, the most prescribed lysosomotropic drugs are proton pump inhibitors (PPIs), chloroquine (CQ), and the related hydroxychloroquine (HCQ), which belong to the group of disease-modifying antirheumatic drugs (DMARDs). This commentary aims to open the discussion on the possible mechanisms connecting the long-term prescribing of these drugs to the elderly and the incidence of neurodegenerative diseases.
MeSH term(s)	Mice ; Animals ; Autophagy/physiology ; Alzheimer Disease/drug therapy ; Alzheimer Disease/metabolism ; Parkinson Disease/drug therapy ; Parkinson Disease/metabolism ; Amyloid Precursor Protein Secretases/metabolism ; Antirheumatic Agents/pharmacology ; Amyloid beta-Peptides/metabolism ; Hydroxychloroquine/adverse effects ; Aspartic Acid Endopeptidases/metabolism ; Aspartic Acid Endopeptidases/pharmacology ; Neurodegenerative Diseases/metabolism ; Lysosomes/metabolism ; Class III Phosphatidylinositol 3-Kinases/metabolism ; Chloroquine/pharmacology ; Hydrogen-Ion Concentration
Chemical Substances	Amyloid Precursor Protein Secretases (EC 3.4.-) ; Antirheumatic Agents ; Amyloid beta-Peptides ; Hydroxychloroquine (4QWG6N8QKH) ; Aspartic Acid Endopeptidases (EC 3.4.23.-) ; Class III Phosphatidylinositol 3-Kinases (EC 2.7.1.137) ; Chloroquine (886U3H6UFF)
Language	English
Publishing date	2023-07-23
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2454135-7
ISSN	1554-8635 ; 1554-8627
ISSN (online)	1554-8635
ISSN	1554-8627
DOI	10.1080/15548627.2023.2214960
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