Pyridoxal kinase and poly(ADP-ribose) affect the immune microenvironment of locally advanced cancers

Adrien Joseph; Juncheng Pan; Judith Michels; Guido Kroemer; Maria Castedo

doi:10.1080/2162402X.2021.1950954

Pyridoxal kinase and poly(ADP-ribose) affect the immune microenvironment of locally advanced cancers

Oncoimmunology. 2021 Jul 8;10(1):1950954. doi: 10.1080/2162402X.2021.1950954. eCollection 2021.

Authors

Adrien Joseph^{1

2

3}, Juncheng Pan^{1

2

3}, Judith Michels⁴, Guido Kroemer^{1

2

5

6

7

8}, Maria Castedo^{1

2}

Affiliations

¹ Equipe 11 labellisée par la Ligue contre le Cancer, Université de Paris, Sorbonne Université, INSERM U1138, Centre de Recherche des Cordeliers, Paris, France.
² Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France.
³ Faculté de médecine, Université de Paris Saclay, Kremlin Bicêtre, France.
⁴ Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France.
⁵ Paris Descartes University, Sorbonne Paris Cité, Paris, France.
⁶ Pôle de Biologie, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France.
⁷ Suzhou Institute for Systems Medicine, Chinese Academy of Medical Sciences, Suzhou, China.
⁸ Karolinska Institute, Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, Sweden.

Abstract

Malignant cells adapt to the hostile tumor microenvironment by escaping from, or actively suppressing, anticancer immune responses. In the past, we reported that reduced synthesis of active vitamin B6 (due to downregulation of pyridoxal kinase) or overactivation of poly(ADP-ribose) polymerase confers resistance to chemotherapy with cisplatin. Recently, we found that these prognostically adverse alterations in oncometabolism also correlate with the rarefaction of immune effectors in the tumor bed.

Keywords: CD8+ T cells; Tumor microenvironment; cervical cancer; dendritic cells; immune escape; immunotherapy; metabolism; non-small cell lung cancer; survival; vitamin B.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cisplatin / therapeutic use
Humans
Neoplasms* / drug therapy
Neoplasms* / immunology
Poly Adenosine Diphosphate Ribose*
Poly(ADP-ribose) Polymerases
Pyridoxal Kinase
Tumor Microenvironment / immunology*

Substances

Poly Adenosine Diphosphate Ribose
Poly(ADP-ribose) Polymerases
Pyridoxal Kinase
Cisplatin

Grants and funding

GK is supported by the Ligue contre le Cancer (équipe labellisée); Agence National de la Recherche (ANR) – Projets blancs; ANR under the frame of E-Rare-2, the ERA-Net for Research on Rare Diseases; AMMICa US23/CNRS UMS3655; Association pour la recherche sur le cancer (ARC); Association “Ruban Rose”; Cancéropôle Ile-de-France; Chancelerie des universités de Paris (Legs Poix), Fondation pour la Recherche Médicale (FRM); a donation by Elior; European Research Area Network on Cardiovascular Diseases (ERA-CVD, MINOTAUR); Gustave Roussy Odyssea, the European Union Horizon 2020 Project Oncobiome; Fondation Carrefour; High-end Foreign Expert Program in China [GDW20171100085], Institut National du Cancer (INCa); Inserm (HTE); Institut Universitaire de France; LeDucq Foundation; the LabEx Immuno-Oncology (ANR-18-IDEX-0001); the RHU Torino Lumière; the Seerave Foundation; the SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); and the SIRIC Cancer Research and Personalized Medicine (CARPEM). AJ is supported by a grant from Fondation ARC pour la Recherche sur le Cancer. This study contributes to the IdEx Université de Paris ANR-18-IDEX-0001.