CAR-T Cells Hit the Tumor Microenvironment: Strategies to Overcome Tumor Escape

Autor: Asis Palazon, Daniel J. Powell, Alba Rodriguez-Garcia, Sonia Guedan, Estela Noguera-Ortega
Rok vydání: 2020
Předmět:
0301 basic medicine
adoptive cell transfer (ACT)
medicine.medical_treatment
Immunoteràpia
Review
Immunotherapy
Adoptive
T-Lymphocytes
Regulatory
Cell therapy
Mice
0302 clinical medicine
Neoplasms
Tumor Microenvironment
Immunology and Allergy
Medicine
Receptors
Chimeric Antigen
solid tumors
Extracellular Matrix
3. Good health
medicine.anatomical_structure
Cèl·lules T
Immunosupressors
immunotherapy
chimeric antigen receptors (CAR)
lcsh:Immunologic diseases. Allergy
T cell
Immunology
T cells
Immunotheraphy
03 medical and health sciences
Lymphocytes
Tumor-Infiltrating
Immune system
Antigen
Animals
Humans
Tumors
Tumor microenvironment
immunosuppressive tumor microenvironment
business.industry
Macrophages
Myeloid-Derived Suppressor Cells
Models
Immunological
Immunosupressive agents
Immunotherapy
Fibroblasts
Immune Checkpoint Proteins
Chimeric antigen receptor
030104 developmental biology
inhibitory receptors
Tumor Escape
Cancer research
Tumor Hypoxia
business
lcsh:RC581-607
030215 immunology
Zdroj: Dipòsit Digital de la UB
Universidad de Barcelona
Frontiers in Immunology, Vol 11 (2020)
Frontiers in Immunology
Popis: Chimeric antigen receptor (CAR) T cell therapies have demonstrated remarkable efficacy for the treatment of hematological malignancies. However, in patients with solid tumors, objective responses to CAR-T cell therapy remain sporadic and transient. A major obstacle for CAR-T cells is the intrinsic ability of tumors to evade immune responses. Advanced solid tumors are largely composed of desmoplastic stroma and immunosuppressive modulators, and characterized by aberrant cell proliferation and vascularization, resulting in hypoxia and altered nutrient availability. To mount a curative response after infusion, CAR-T cells must infiltrate the tumor, recognize their cognate antigen and perform their effector function in this hostile tumor microenvironment, to then differentiate and persist as memory T cells that confer long-term protection. Fortunately, recent advances in synthetic biology provide a wide set of tools to genetically modify CAR-T cells to overcome some of these obstacles. In this review, we provide a comprehensive overview of the key tumor intrinsic mechanisms that prevent an effective CAR-T cell antitumor response and we discuss the most promising strategies to prevent tumor escape to CAR-T cell therapy.
Databáze: OpenAIRE
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