Review
Beyond the concept of cold and hot tumors for the development of novel predictive biomarkers and the rational design of immunotherapy combination
Eleonore De Guillebon,
Antoine Dardenne,
Antonin Saldmann,
Sylvie Séguier,
Thi Tran, Lea Paolini, Celeste Lebbe,
Eric Tartour,
Eleonore De Guillebon
Department of Medical Oncology, Institut Curie, Paris, France
Search for more papers by this authorAntoine Dardenne
Department of Gastro-enterology and Gastro-intestinal Oncology, Hopital Européen Georges Pompidou, APHP, Paris, France
Search for more papers by this authorAntonin Saldmann
Université de Paris, PARCC, INSERM, Paris, France
Department of Immunology, AP-HP, Hopital Européen Georges Pompidou, Paris, France
Search for more papers by this authorSylvie Séguier
Université de Paris, PARCC, INSERM, Paris, France
Faculté de Chirurgie Dentaire, Hôpital Louis Mourier, Montrouge, France
Search for more papers by this authorCeleste Lebbe
Department of Dermatology, Saint-Louis University Hospital, Paris, France
Université de Paris, INSERM U976, Paris, France
Search for more papers by this authorCorresponding Author
Eric Tartour
Université de Paris, PARCC, INSERM, Paris, France
Department of Immunology, AP-HP, Hopital Européen Georges Pompidou, Paris, France
Equipe Labellisée Ligue Contre le Cancer, Paris, France
Correspondence to: Eleonore de Guillebon, E-mail: [email protected] or Eric Tartour, E-mail: [email protected]Search for more papers by this authorEleonore De Guillebon,
Antoine Dardenne,
Antonin Saldmann,
Sylvie Séguier,
Thi Tran, Lea Paolini, Celeste Lebbe,
Eric Tartour,
Eleonore De Guillebon
Department of Medical Oncology, Institut Curie, Paris, France
Search for more papers by this authorAntoine Dardenne
Department of Gastro-enterology and Gastro-intestinal Oncology, Hopital Européen Georges Pompidou, APHP, Paris, France
Search for more papers by this authorAntonin Saldmann
Université de Paris, PARCC, INSERM, Paris, France
Department of Immunology, AP-HP, Hopital Européen Georges Pompidou, Paris, France
Search for more papers by this authorSylvie Séguier
Université de Paris, PARCC, INSERM, Paris, France
Faculté de Chirurgie Dentaire, Hôpital Louis Mourier, Montrouge, France
Search for more papers by this authorCeleste Lebbe
Department of Dermatology, Saint-Louis University Hospital, Paris, France
Université de Paris, INSERM U976, Paris, France
Search for more papers by this authorCorresponding Author
Eric Tartour
Université de Paris, PARCC, INSERM, Paris, France
Department of Immunology, AP-HP, Hopital Européen Georges Pompidou, Paris, France
Equipe Labellisée Ligue Contre le Cancer, Paris, France
Correspondence to: Eleonore de Guillebon, E-mail: [email protected] or Eric Tartour, E-mail: [email protected]Search for more papers by this authorAbstract
Immunotherapy has revolutionized the management of cancers. At the end of 2018, 1,716 clinical trials assessed regimen that combine program death-1 (PD-1)/program death ligand-1 (PD-L1) blockers with other cancer therapies (tyrosine kinase inhibitor, chemotherapy and radiotherapy). There is a contrast between these clinical dynamics and the difficulty of identifying biomarkers to better select patients that could benefit from immunotherapy. In this context, different tumor classifications have been proposed to try to better stratify patients. They rely on the characteristics of the tumor microenvironment and led first to divide them into hot and cold tumors. In this review, we aim to demonstrate the limitations of this classification focusing on the differential significance of subpopulations of intratumor CD8 + T cells. We also underline novel mechanisms of resistance to anti-PD-1/PD-L1 blockade, focusing on myeloid cells, hypoxia and tumor immunoediting under treatment. Understanding the mechanisms of resistance to immune-checkpoint inhibitor is indeed a powerful research driver that allows further identification of novel biomarkers, drug development and bring a rational to innovative therapeutic combinations.
Conflict of interest
Celeste Lebbe declares potential financial conflict of interest: Research grants (BMS, Roche), Honoraria (BMS, MSD, Novartis, Amgen, Roche, Pierre-Fabre, Pfizer, Incyte), Consultancy (BMS, MSD, Novartis, Amgen, Roche, Merck-Serono, Sanofi), Speakers bureau (BMS, MSD, Novartis, Amgen, Roche), Travel accommodations-meetings (BMS), Advisory board (BMS, Novartis, Amgen, Roche), Board (Avantis), advisory role (BMS, MSD, Novartis, Roche). Eric Tartour declares a potential conflict of interest: Research grants (Servier, Vaxeal), Honoraria (BMS, Merck-MSD), Advisory Board (BMS, Astra-Zeneca).
Supporting Information
| Filename | Description |
|---|---|
| ijc32889-sup-0001-TableS1.pdfPDF document, 22.3 KB | Table S1 Description of the various IFNγ signatures |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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