Cold Tumors: A Therapeutic Challenge for Immunotherapy

Therapeutic monoclonal antibodies targeting immune checkpoints (ICPs) have changed the treatment landscape of many tumors. However, response rate remains relatively low in most cases. A major factor involved in initial resistance to ICP inhibitors is the lack or paucity of tumor T cell infiltration,...

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Bibliographic Details
Published in:Frontiers in immunology 2019, Vol.10, p.168-168
Main Authors: Bonaventura, Paola, Shekarian, Tala, Alcazer, Vincent, Valladeau-Guilemond, Jenny, Valsesia-Wittmann, Sandrine, Amigorena, Sebastian, Caux, Christophe, Depil, Stéphane
Format: Article
Language:English
Subjects:
Antibodies, Bispecific - therapeutic use
Antibodies, Monoclonal - therapeutic use
Antigen-Presenting Cells - immunology
Antigens, Neoplasm - immunology
Cancer
Cancer Vaccines - therapeutic use
CD8-Positive T-Lymphocytes - immunology
cold tumors
Cytokines - metabolism
Cytokines - therapeutic use
Humans
Immunology
Immunotherapy
Immunotherapy, Adoptive
Life Sciences
Lymphocyte Activation
Lymphocytes, Tumor-Infiltrating - immunology
Neoplasms - immunology
Neoplasms - therapy
Oncolytic Virotherapy
priming
T cells
trafficking
tumor antigen
Tumor Microenvironment - immunology
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Summary:Therapeutic monoclonal antibodies targeting immune checkpoints (ICPs) have changed the treatment landscape of many tumors. However, response rate remains relatively low in most cases. A major factor involved in initial resistance to ICP inhibitors is the lack or paucity of tumor T cell infiltration, characterizing the so-called "cold tumors." In this review, we describe the main mechanisms involved in the absence of T cell infiltration, including lack of tumor antigens, defect in antigen presentation, absence of T cell activation and deficit of homing into the tumor bed. We discuss then the different therapeutic approaches that could turn cold into hot tumors. In this way, specific therapies are proposed according to their mechanism of action. In addition, ''supra-physiological'' therapies, such as T cell recruiting bispecific antibodies and Chimeric Antigen Receptor (CAR) T cells, may be active regardless of the mechanism involved, especially in MHC class I negative tumors. The determination of the main factors implicated in the lack of preexisting tumor T cell infiltration is crucial for the development of adapted algorithms of treatments for cold tumors.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2019.00168