Version 1
: Received: 29 August 2024 / Approved: 31 August 2024 / Online: 2 September 2024 (13:12:50 CEST)
How to cite:
Singh, K. P.; Singh, A.; Wolkenhauer, O.; Gupta, S. K. Regulatory Role of IL-6 in Immune-Related Adverse Events During Checkpoint Inhibitor Treatment in Melanoma. Preprints2024, 2024090006. https://doi.org/10.20944/preprints202409.0006.v1
Singh, K. P.; Singh, A.; Wolkenhauer, O.; Gupta, S. K. Regulatory Role of IL-6 in Immune-Related Adverse Events During Checkpoint Inhibitor Treatment in Melanoma. Preprints 2024, 2024090006. https://doi.org/10.20944/preprints202409.0006.v1
Singh, K. P.; Singh, A.; Wolkenhauer, O.; Gupta, S. K. Regulatory Role of IL-6 in Immune-Related Adverse Events During Checkpoint Inhibitor Treatment in Melanoma. Preprints2024, 2024090006. https://doi.org/10.20944/preprints202409.0006.v1
APA Style
Singh, K. P., Singh, A., Wolkenhauer, O., & Gupta, S. K. (2024). Regulatory Role of IL-6 in Immune-Related Adverse Events During Checkpoint Inhibitor Treatment in Melanoma. Preprints. https://doi.org/10.20944/preprints202409.0006.v1
Chicago/Turabian Style
Singh, K. P., Olaf Wolkenhauer and Shailendra Kumar Gupta. 2024 "Regulatory Role of IL-6 in Immune-Related Adverse Events During Checkpoint Inhibitor Treatment in Melanoma" Preprints. https://doi.org/10.20944/preprints202409.0006.v1
Abstract
The landscape of clinical management for metastatic melanoma (MM) and other solid tumors has been modernized by the advent of immune checkpoint inhibitors (ICI), including programmed cell death-1 (PD-1), programmed cell death-ligand 1 (PD-L1), and cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitors. While these agents demonstrate efficacy in suppressing tumor growth, they also lead to immune-related adverse events (irAEs), resulting in exacerbation of autoimmune diseases such as Rheumatoid arthritis (RA), Ulcerative colitis (UC), and Crohn’s disease (CD). The immune checkpoint inhibitors offer promising advancements in the treatment of melanoma and other cancers, but they also present significant challenges related to irAEs and autoimmune diseases. Ongoing research is crucial to better understand these challenges and develop strategies for mitigating adverse effects while maximizing therapeutic benefits. In this manuscript, we addressed this challenge using network-based approaches by constructing and analyzing molecular and signaling networks associated with tumor-immune cross-talk.. Our analysis revealed that IL6 is the key regulator responsible for irAEs during ICI therapies. Furthermore, we conducted an integrative network and molecular-level analysis, including virtual screening, of drug libraries, such as the Collection of Open Natural Products (COCONUT) and the Zinc15 FDA-approved library, to identify potential IL-6 inhibitors.. Subsequently, the compound amprenavir was identified as the best molecule that may disrupt essential interactions between IL6 and IL6R responsible for initiating signaling cascades underlying irAEs in ICI therapies.
Biology and Life Sciences, Biology and Biotechnology
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.
