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Identification of immune-related mechanisms of cetuximab induced skin toxicity in colorectal cancer patients

Skin rash is a well-known predictive marker of the response to cetuximab (Cmab) in metastatic colorectal cancer (mCRC). However, the mechanism of skin rash development is not well understood. Following exposure to EGFR-targeted therapies, changes in IL-8 levels have been reported. The aim of this st...

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Autores principales: Park, Jin Hyun, Kim, Mi Young, Choi, In Sil, Kim, Ji-Won, Kim, Jin Won, Lee, Keun-Wook, Kim, Jin-Soo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9586384/
https://www.ncbi.nlm.nih.gov/pubmed/36269747
http://dx.doi.org/10.1371/journal.pone.0276497
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author Park, Jin Hyun
Kim, Mi Young
Choi, In Sil
Kim, Ji-Won
Kim, Jin Won
Lee, Keun-Wook
Kim, Jin-Soo
author_facet Park, Jin Hyun
Kim, Mi Young
Choi, In Sil
Kim, Ji-Won
Kim, Jin Won
Lee, Keun-Wook
Kim, Jin-Soo
author_sort Park, Jin Hyun
collection PubMed
description Skin rash is a well-known predictive marker of the response to cetuximab (Cmab) in metastatic colorectal cancer (mCRC). However, the mechanism of skin rash development is not well understood. Following exposure to EGFR-targeted therapies, changes in IL-8 levels have been reported. The aim of this study was to evaluate the association between skin rash and inflammatory cytokine levels, including IL-8. Between 2014 and 2017, we prospectively enrolled 38 mCRC patients who underwent chemotherapy with either Cmab or bevacizumab (Bmab) at two hospitals. We performed multiplex cytokine ELISA with 20 inflammatory cytokines including E-selectin, GM-CSF, IFN-alpha, IFN-γ, IL-1 alpha, IL-1 beta, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17A, IP-10, MCP-1, MIP-1 alpha, MIP-1 beta, P-selectin, sICAM-1, and TNF-alpha at baseline before cycle 1, 24 h after cycle 1, before cycle 2 (= 14 d), and before cycle 3 (= 28 d). Cytokine levels were compared using ANOVA after log-transformation. IL-8 genotypes in 30 patients treated with Cmab were determined using the polymerase chain reaction restriction fragment length polymorphism technique. Depending on the RAS mutational status, 30 and eight patients were treated with Cmab and Bmab-based chemotherapy, respectively. Skin rash developed in 23 (76.6%) of the 30 patients treated with Cmab plus FOLFIRI, after cycle 1. Only the mean log-transformed serum IL-8 level in patients with skin toxicity was statistically lower (2.83 ± 0.15) than in patients who did not experience skin toxicity (3.65 ± 0.27) and received Bmab (3.10 ± 0.26) (ANOVA test, p value = 0.0341). In addition, IL-8 polymorphism did not affect IL-8 levels, skin toxicity, or tumor response in Cmab treated patients. This study suggests that the inflammatory cytokine levels might be affected by Cmab exposure and are associated with the development of skin rash in mCRC patients. Further studies are warranted to evaluate this interaction in Cmab treated patients.
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spelling pubmed-95863842022-10-22 Identification of immune-related mechanisms of cetuximab induced skin toxicity in colorectal cancer patients Park, Jin Hyun Kim, Mi Young Choi, In Sil Kim, Ji-Won Kim, Jin Won Lee, Keun-Wook Kim, Jin-Soo PLoS One Research Article Skin rash is a well-known predictive marker of the response to cetuximab (Cmab) in metastatic colorectal cancer (mCRC). However, the mechanism of skin rash development is not well understood. Following exposure to EGFR-targeted therapies, changes in IL-8 levels have been reported. The aim of this study was to evaluate the association between skin rash and inflammatory cytokine levels, including IL-8. Between 2014 and 2017, we prospectively enrolled 38 mCRC patients who underwent chemotherapy with either Cmab or bevacizumab (Bmab) at two hospitals. We performed multiplex cytokine ELISA with 20 inflammatory cytokines including E-selectin, GM-CSF, IFN-alpha, IFN-γ, IL-1 alpha, IL-1 beta, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17A, IP-10, MCP-1, MIP-1 alpha, MIP-1 beta, P-selectin, sICAM-1, and TNF-alpha at baseline before cycle 1, 24 h after cycle 1, before cycle 2 (= 14 d), and before cycle 3 (= 28 d). Cytokine levels were compared using ANOVA after log-transformation. IL-8 genotypes in 30 patients treated with Cmab were determined using the polymerase chain reaction restriction fragment length polymorphism technique. Depending on the RAS mutational status, 30 and eight patients were treated with Cmab and Bmab-based chemotherapy, respectively. Skin rash developed in 23 (76.6%) of the 30 patients treated with Cmab plus FOLFIRI, after cycle 1. Only the mean log-transformed serum IL-8 level in patients with skin toxicity was statistically lower (2.83 ± 0.15) than in patients who did not experience skin toxicity (3.65 ± 0.27) and received Bmab (3.10 ± 0.26) (ANOVA test, p value = 0.0341). In addition, IL-8 polymorphism did not affect IL-8 levels, skin toxicity, or tumor response in Cmab treated patients. This study suggests that the inflammatory cytokine levels might be affected by Cmab exposure and are associated with the development of skin rash in mCRC patients. Further studies are warranted to evaluate this interaction in Cmab treated patients. Public Library of Science 2022-10-21 /pmc/articles/PMC9586384/ /pubmed/36269747 http://dx.doi.org/10.1371/journal.pone.0276497 Text en © 2022 Park et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Park, Jin Hyun
Kim, Mi Young
Choi, In Sil
Kim, Ji-Won
Kim, Jin Won
Lee, Keun-Wook
Kim, Jin-Soo
Identification of immune-related mechanisms of cetuximab induced skin toxicity in colorectal cancer patients
title Identification of immune-related mechanisms of cetuximab induced skin toxicity in colorectal cancer patients
title_full Identification of immune-related mechanisms of cetuximab induced skin toxicity in colorectal cancer patients
title_fullStr Identification of immune-related mechanisms of cetuximab induced skin toxicity in colorectal cancer patients
title_full_unstemmed Identification of immune-related mechanisms of cetuximab induced skin toxicity in colorectal cancer patients
title_short Identification of immune-related mechanisms of cetuximab induced skin toxicity in colorectal cancer patients
title_sort identification of immune-related mechanisms of cetuximab induced skin toxicity in colorectal cancer patients
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9586384/
https://www.ncbi.nlm.nih.gov/pubmed/36269747
http://dx.doi.org/10.1371/journal.pone.0276497
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