Version 1
: Received: 1 October 2024 / Approved: 2 October 2024 / Online: 2 October 2024 (10:58:43 CEST)
How to cite:
Malhotra, J.; Huang, A.; Amini, A.; Lee, P. Therapeutic Strategies to Target Immunotherapy Resistance in Non-Small Cell Lung Cancer (NSCLC). Preprints2024, 2024100155. https://doi.org/10.20944/preprints202410.0155.v1
Malhotra, J.; Huang, A.; Amini, A.; Lee, P. Therapeutic Strategies to Target Immunotherapy Resistance in Non-Small Cell Lung Cancer (NSCLC). Preprints 2024, 2024100155. https://doi.org/10.20944/preprints202410.0155.v1
Malhotra, J.; Huang, A.; Amini, A.; Lee, P. Therapeutic Strategies to Target Immunotherapy Resistance in Non-Small Cell Lung Cancer (NSCLC). Preprints2024, 2024100155. https://doi.org/10.20944/preprints202410.0155.v1
APA Style
Malhotra, J., Huang, A., Amini, A., & Lee, P. (2024). Therapeutic Strategies to Target Immunotherapy Resistance in Non-Small Cell Lung Cancer (NSCLC). Preprints. https://doi.org/10.20944/preprints202410.0155.v1
Chicago/Turabian Style
Malhotra, J., Arya Amini and Percy Lee. 2024 "Therapeutic Strategies to Target Immunotherapy Resistance in Non-Small Cell Lung Cancer (NSCLC)" Preprints. https://doi.org/10.20944/preprints202410.0155.v1
Abstract
Immunotherapy with programmed Cell Death Protein/Programmed Cell Death Ligand 1 (PD-1/PD-L1) targeting antibodies has transformed clinical outcomes for patients with non-small cell lung cancer (NSCLC) and has become an integral part of standard treatment regimens. However, the response to PD-1/PD-L1 inhibitors varies, and many tumors present with either primary or acquired resistance to immunotherapy. There are emerging data on potential mechanisms underlying resistance to immunotherapy which is derived mainly from either preclinical studies or secondary correlative analyses from clinical trials. Resistance to immunotherapy is complex and can present immediately after treatment initiation (primary resistance) or after initial clinical benefit (secondary or acquired resistance). The tumor microenvironment, particularly the presence, and activity of T cells, also significantly influences resistance with both tumor-extrinsic as well as tumor-intrinsic mechanisms such as lack of T-cell infiltration, insufficient neoantigens, or absence of an interferon signature identified as being associated with ICI resistance. Improved understanding of the molecular and immunologic mechanisms underlying immunotherapy resistance is essential for the future development of effective therapies targeting immunotherapy resistance. In this review, we discuss the emerging data identifying the molecular mechanisms of primary resistance to immunotherapy and explore potential therapeutic strategies to target these.
Keywords
primary resistance; immunotherapy
Subject
Medicine and Pharmacology, Oncology and Oncogenics
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
