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Targeting IL-23 for the interception of obesity-associated colorectal cancer
Inflammation and obesity are two major factors that promote Colorectal cancer (CRC). Our recent data suggests that interleukin (IL)-23, is significantly elevated in CRC tumors and correlates with patient obesity, tumor grade and survival. Thus, we hypothesize that obesity and CRC may be linked via i...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Neoplasia Press
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10568285/ https://www.ncbi.nlm.nih.gov/pubmed/37813000 http://dx.doi.org/10.1016/j.neo.2023.100939 |
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author | Madka, Venkateshwar Chiliveru, Srikanth Panneerselvam, Janani Pathuri, Gopal Zhang, Yuting Stratton, Nicole Kumar, Nandini Sanghera, Dharambir K. Rao, Chinthalapally V. |
author_facet | Madka, Venkateshwar Chiliveru, Srikanth Panneerselvam, Janani Pathuri, Gopal Zhang, Yuting Stratton, Nicole Kumar, Nandini Sanghera, Dharambir K. Rao, Chinthalapally V. |
author_sort | Madka, Venkateshwar |
collection | PubMed |
description | Inflammation and obesity are two major factors that promote Colorectal cancer (CRC). Our recent data suggests that interleukin (IL)-23, is significantly elevated in CRC tumors and correlates with patient obesity, tumor grade and survival. Thus, we hypothesize that obesity and CRC may be linked via inflammation and IL-23 may be a potential target for intervention in high-risk patients. TCGA dataset and patient sera were evaluated for IL-23A levels. IL-23A [IL-23 p19(−/−)] knockout (KO) mice were crossed to Apc(min/+) mice and progeny were fed low-fat or high-fat diets. At termination intestines were evaluated for tumorigenesis. Tumors, serum, and fecal contents were analyzed for protein biomarkers, cytokines, and microbiome profile respectively. IL-23A levels are elevated in the sera of patients with obesity and colon tumors. Genetic ablation of IL-23A significantly suppressed colonic tumor multiplicity (76–96 %) and incidence (72–95 %) in male and female mice. Similarly, small-intestinal tumor multiplicity and size were also significantly reduced in IL-23A KO mice. IL-23A knockdown in Apc(min/+) mice fed high-fat diet, also resulted in significant suppression of colonic (50–58 %) and SI (41–48 %) tumor multiplicity. Cytokine profiling showed reduction in several circulating pro-inflammatory cytokines including loss of IL-23A. Biomarker analysis suggested reduced tumor cell proliferation and immune modulation with an increase in tumor-infiltrating CD4+ and CD8+ T-lymphocytes in the IL-23A KO mice compared to controls. Fecal microbiome analysis revealed potentially beneficial changes in the bacterial population profile. In summary, our data indicates a tumor promoting role for IL-23 in CRC including diet-induced obesity. With several IL-23 targeted therapies in clinical trials, there is a great potential for targeting this cytokine for CRC prevention and therapy. |
format | Online Article Text |
id | pubmed-10568285 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Neoplasia Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-105682852023-10-13 Targeting IL-23 for the interception of obesity-associated colorectal cancer Madka, Venkateshwar Chiliveru, Srikanth Panneerselvam, Janani Pathuri, Gopal Zhang, Yuting Stratton, Nicole Kumar, Nandini Sanghera, Dharambir K. Rao, Chinthalapally V. Neoplasia Original article Inflammation and obesity are two major factors that promote Colorectal cancer (CRC). Our recent data suggests that interleukin (IL)-23, is significantly elevated in CRC tumors and correlates with patient obesity, tumor grade and survival. Thus, we hypothesize that obesity and CRC may be linked via inflammation and IL-23 may be a potential target for intervention in high-risk patients. TCGA dataset and patient sera were evaluated for IL-23A levels. IL-23A [IL-23 p19(−/−)] knockout (KO) mice were crossed to Apc(min/+) mice and progeny were fed low-fat or high-fat diets. At termination intestines were evaluated for tumorigenesis. Tumors, serum, and fecal contents were analyzed for protein biomarkers, cytokines, and microbiome profile respectively. IL-23A levels are elevated in the sera of patients with obesity and colon tumors. Genetic ablation of IL-23A significantly suppressed colonic tumor multiplicity (76–96 %) and incidence (72–95 %) in male and female mice. Similarly, small-intestinal tumor multiplicity and size were also significantly reduced in IL-23A KO mice. IL-23A knockdown in Apc(min/+) mice fed high-fat diet, also resulted in significant suppression of colonic (50–58 %) and SI (41–48 %) tumor multiplicity. Cytokine profiling showed reduction in several circulating pro-inflammatory cytokines including loss of IL-23A. Biomarker analysis suggested reduced tumor cell proliferation and immune modulation with an increase in tumor-infiltrating CD4+ and CD8+ T-lymphocytes in the IL-23A KO mice compared to controls. Fecal microbiome analysis revealed potentially beneficial changes in the bacterial population profile. In summary, our data indicates a tumor promoting role for IL-23 in CRC including diet-induced obesity. With several IL-23 targeted therapies in clinical trials, there is a great potential for targeting this cytokine for CRC prevention and therapy. Neoplasia Press 2023-10-07 /pmc/articles/PMC10568285/ /pubmed/37813000 http://dx.doi.org/10.1016/j.neo.2023.100939 Text en © 2023 The Authors. Published by Elsevier Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original article Madka, Venkateshwar Chiliveru, Srikanth Panneerselvam, Janani Pathuri, Gopal Zhang, Yuting Stratton, Nicole Kumar, Nandini Sanghera, Dharambir K. Rao, Chinthalapally V. Targeting IL-23 for the interception of obesity-associated colorectal cancer |
title | Targeting IL-23 for the interception of obesity-associated colorectal cancer |
title_full | Targeting IL-23 for the interception of obesity-associated colorectal cancer |
title_fullStr | Targeting IL-23 for the interception of obesity-associated colorectal cancer |
title_full_unstemmed | Targeting IL-23 for the interception of obesity-associated colorectal cancer |
title_short | Targeting IL-23 for the interception of obesity-associated colorectal cancer |
title_sort | targeting il-23 for the interception of obesity-associated colorectal cancer |
topic | Original article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10568285/ https://www.ncbi.nlm.nih.gov/pubmed/37813000 http://dx.doi.org/10.1016/j.neo.2023.100939 |
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