Immunologic tumor microenvironment modulators for turning cold tumors hot

Tumors can be classified into distinct immunophenotypes based on the presence and arrangement of cytotoxic immune cells within the tumor microenvironment (TME). Hot tumors, characterized by heightened immune activity and responsiveness to immune checkpoint inhibitors (ICIs), stand in stark contrast...

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Bibliographic Details
Published in:Cancer communications (London, England) England), 2024-05, Vol.44 (5), p.521-553
Main Authors: Khosravi, Gholam‐Reza, Mostafavi, Samaneh, Bastan, Sanaz, Ebrahimi, Narges, Gharibvand, Roya Safari, Eskandari, Nahid
Format: Article
Language:English
Subjects:
Animals
cold tumor
hot tumor
Humans
Immune Checkpoint Inhibitors - therapeutic use
immunologic modulator
immunotherapy
Immunotherapy - methods
Neoplasms - immunology
Neoplasms - therapy
Review
therapeutic strategy
tumor microenvironment
Tumor Microenvironment - immunology
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Summary:Tumors can be classified into distinct immunophenotypes based on the presence and arrangement of cytotoxic immune cells within the tumor microenvironment (TME). Hot tumors, characterized by heightened immune activity and responsiveness to immune checkpoint inhibitors (ICIs), stand in stark contrast to cold tumors, which lack immune infiltration and remain resistant to therapy. To overcome immune evasion mechanisms employed by tumor cells, novel immunologic modulators have emerged, particularly ICIs targeting cytotoxic T‐lymphocyte‐associated protein 4 (CTLA‐4) and programmed cell death protein 1/programmed death‐ligand 1(PD‐1/PD‐L1). These agents disrupt inhibitory signals and reactivate the immune system, transforming cold tumors into hot ones and promoting effective antitumor responses. However, challenges persist, including primary resistance to immunotherapy, autoimmune side effects, and tumor response heterogeneity. Addressing these challenges requires innovative strategies, deeper mechanistic insights, and a combination of immune interventions to enhance the effectiveness of immunotherapies. In the landscape of cancer medicine, where immune cold tumors represent a formidable hurdle, understanding the TME and harnessing its potential to reprogram the immune response is paramount. This review sheds light on current advancements and future directions in the quest for more effective and safer cancer treatment strategies, offering hope for patients with immune‐resistant tumors.
ISSN:2523-3548
2523-3548
DOI:10.1002/cac2.12539