Immune Checkpoint Inhibitors and Immune Checkpoint Resistance
A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".
Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 17466
Special Issue Editor
Interests: breast cancer; endocrine therapy resistance; immunotherapy; immunocheckpoint inhibitors; immunocheckpoint resistance; cardiotoxicity/cardioncology; notch inhibitors
Special Issue Information
Dear Colleagues,
The immuno-oncology era (IO) has achieved many successes and represents an important milestone for cancer treatment. Immune checkpoints are important regulators of immune activation, and they play a key role in maintaining immune balance and preventing autoimmune diseases. Therefore, immune checkpoint inhibitors (ICIs) have led to a revolution in the management of many tumor types, such as melanoma, non-small cell lung cancer (NSCLC), kidney cancer, and bladder/urothelial cancer. Starting with the approval of anti-cytotoxic T lymphocyte-associated protein 4 (anti-CTLA-4) for advanced-stage melanoma in 2011, other antibodies against programmed cell death 1 (PD-1) and its ligand (PD-L1) quickly gained US Food and Drug Administration (FDA) approval for the treatment of a wide array of cancer types, demonstrating a statistically significant increase in overall survival. Considering the remarkable efficacy of IO in clinical trials, the FDA has approved a variety of immune checkpoint inhibitors for the treatment of advanced tumors, first as monotherapy, and later in combination. In clinical research, the number of IO targets in development has risen from 265 in 2017 to 469 in 2019 (“Clinical Challenges of Immune Checkpoint Inhibitors”. Maria de Miguel and Emialiano Calvo, Cancer Cell https://0-doi-org.brum.beds.ac.uk/10.1016/j.ccell.2020.07.004).
In addition to the abovementioned classical immune checkpoints (anti-CTL4, anti-PD1, anti-PD-L1), a number of immune checkpoint pathways have been discovered with different mechanisms of action, such as LAG 3 and T cell immunoglobulin mucin 3 (Tim-3). The inhibition of both LAG 3 and PD-1 can reverse the depletion of lymphocytes, thereby enhancing the immune response, while the blockade of Tim-3 can enhance the antitumor effect of PD-1 inhibitors.
However, despite the success of ICIs, resistance to these agents restricts the number of patients able to achieve durable responses, and immune-related adverse events can complicate treatment. Thus, a better understanding of the requirements for an effective and safe antitumor immune response following ICI therapy is needed. Studies of both tumoral and systemic changes in the immune system following ICI therapy have yielded insight into the basis for both efficacy and resistance. The understanding of the mechanisms of resistance to ICIs represents an important area of investigation in order to be able to combine ICIs with other agents or design new immunotherapies.
Dr. Marzia Adelia Locatelli
Guest Editor
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Keywords
- immune checkpoint inhibitors
- anti-PD-1
- anti-PD-L1
- immune checkpoint resistance
- anti-LAG3
- anti-TIM-3
- primary resistance
- acquired resistance
- immune-related adverse events
- biomarkers
- immunotherapy
- synergistic effect
- PD-1/PD-L1 setting
- tumor microenvironment