دورية أكاديمية
أعرض في EDS

Pexidartinib and Immune Checkpoint Inhibitors Combine to Activate Tumor Immunity in a Murine Colorectal Cancer Model by Depleting M2 Macrophages Differentiated by Cancer-Associated Fibroblasts.

التفاصيل البيبلوغرافية
العنوان: Pexidartinib and Immune Checkpoint Inhibitors Combine to Activate Tumor Immunity in a Murine Colorectal Cancer Model by Depleting M2 Macrophages Differentiated by Cancer-Associated Fibroblasts.
المؤلفون: Shimizu D; Department of Gastroenterology, Hiroshima University Hospital, Hiroshima 734-0037, Japan., Yuge R; Department of Gastroenterology, Hiroshima University Hospital, Hiroshima 734-0037, Japan., Kitadai Y; Department of Gastroenterology, Hiroshima University Hospital, Hiroshima 734-0037, Japan., Ariyoshi M; Department of Gastroenterology, Hiroshima University Hospital, Hiroshima 734-0037, Japan., Miyamoto R; Department of Gastroenterology, Hiroshima University Hospital, Hiroshima 734-0037, Japan., Hiyama Y; Department of Gastroenterology, Hiroshima University Hospital, Hiroshima 734-0037, Japan., Takigawa H; Department of Gastroenterology, Hiroshima University Hospital, Hiroshima 734-0037, Japan., Urabe Y; Department of Gastroenterology, Hiroshima University Hospital, Hiroshima 734-0037, Japan., Oka S; Department of Gastroenterology, Hiroshima University Hospital, Hiroshima 734-0037, Japan.
المصدر: International journal of molecular sciences [Int J Mol Sci] 2024 Jun 26; Vol. 25 (13). Date of Electronic Publication: 2024 Jun 26.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI, [2000-
مواضيع طبية MeSH: Colorectal Neoplasms*/drug therapy , Colorectal Neoplasms*/immunology , Colorectal Neoplasms*/pathology , Colorectal Neoplasms*/metabolism , Cancer-Associated Fibroblasts*/metabolism , Cancer-Associated Fibroblasts*/drug effects , Cancer-Associated Fibroblasts*/immunology , Immune Checkpoint Inhibitors*/pharmacology , Immune Checkpoint Inhibitors*/therapeutic use , Cell Differentiation*/drug effects , Macrophages*/immunology , Macrophages*/metabolism , Macrophages*/drug effects , Tumor Microenvironment*/drug effects , Tumor Microenvironment*/immunology, Animals ; Mice ; Humans ; Aminopyridines/pharmacology ; Aminopyridines/therapeutic use ; Pyrrolidines/pharmacology ; Pyrrolidines/therapeutic use ; Cell Line, Tumor ; Tumor-Associated Macrophages/immunology ; Tumor-Associated Macrophages/drug effects ; Tumor-Associated Macrophages/metabolism ; Disease Models, Animal ; Pyrroles/pharmacology ; Pyrroles/therapeutic use ; Female ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; CD8-Positive T-Lymphocytes/drug effects
مستخلص: Tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs) are known to play supportive roles in tumor development and progression, but their interactions in colorectal cancer (CRC) remain unclear. Here, we investigated the effects of colon-cancer-derived CAFs on TAM differentiation, migration, and tumor immunity, both in vitro and in vivo. When co-cultured with monocytes, CAFs attracted monocytes and induced their differentiation into M2 macrophages. Immunohistology of surgically resected human CRC specimens and orthotopically transplanted mouse tumors revealed a correlation between numbers of CAFs and numbers of M2 macrophages. In a mouse model of CRC orthotopic transplantation, treatment with an inhibitor of the colony-stimulating factor-1 receptor (PLX3397) depleted M2 macrophages and increased CD8-positive T cells infiltrating the tumor nest. While this treatment had a minor effect on tumor growth, combining PLX3397 with anti-PD-1 antibody significantly reduced tumor growth. RNA-seq following combination therapy showed activation of tumor immunity. In summary, CAFs are involved in the induction and mobilization of M2 macrophage differentiation in the CRC tumor immune microenvironment, and the combination of cancer immunotherapy and PLX3397 may represent a novel therapeutic option for CRC.
References: Science. 2014 May 23;344(6186):921-5. (PMID: 24812208)
Carcinogenesis. 2014 Feb;35(2):424-31. (PMID: 24031027)
Front Immunol. 2013 May 31;4:129. (PMID: 23755052)
Nat Rev Clin Oncol. 2017 Jul;14(7):399-416. (PMID: 28117416)
Cancer Res. 2010 Oct 1;70(19):7465-75. (PMID: 20841473)
Nat Rev Immunol. 2011 Oct 14;11(11):723-37. (PMID: 21997792)
Exp Cell Res. 2019 May 15;378(2):131-138. (PMID: 30857971)
Int J Cancer. 2010 Nov 15;127(10):2323-33. (PMID: 20473928)
Cancers (Basel). 2022 Dec 13;14(24):. (PMID: 36551634)
Proc Natl Acad Sci U S A. 2017 Jan 31;114(5):1117-1122. (PMID: 28096371)
Clin Cancer Res. 2018 Nov 1;24(21):5407-5421. (PMID: 29959142)
Cancer Cell. 2014 Jun 16;25(6):846-59. (PMID: 24898549)
Cell Death Dis. 2021 Feb 26;12(2):214. (PMID: 33637678)
Front Immunol. 2019 May 24;10:1084. (PMID: 31178859)
Cancer Immunol Res. 2016 Apr;4(4):312-22. (PMID: 26817997)
Oncogene. 2014 May 8;33(19):2423-31. (PMID: 23728338)
Front Oncol. 2021 Jul 14;11:668349. (PMID: 34336660)
Cell Mol Biol Lett. 2021 Jun 26;26(1):30. (PMID: 34174813)
Cancer Immunol Immunother. 2023 Dec;72(12):3875-3893. (PMID: 37831146)
Cancer Res. 2014 Sep 15;74(18):5057-69. (PMID: 25082815)
N Engl J Med. 2015 Jun 25;372(26):2509-20. (PMID: 26028255)
Blood. 2012 Feb 23;119(8):1810-20. (PMID: 22186992)
J Invest Dermatol. 2010 Jul;130(7):1893-903. (PMID: 20357818)
Clin Cancer Res. 2014 Jun 15;20(12):3146-58. (PMID: 24718867)
Cell Death Dis. 2019 Mar 20;10(4):273. (PMID: 30894509)
Oncoimmunology. 2016 May 24;5(8):e1189052. (PMID: 27622061)
CA Cancer J Clin. 2021 May;71(3):209-249. (PMID: 33538338)
Neoplasia. 2017 May;19(5):429-438. (PMID: 28433772)
Oncol Rep. 2019 Jul;42(1):339-349. (PMID: 31059084)
Proc Natl Acad Sci U S A. 2018 Apr 24;115(17):E4041-E4050. (PMID: 29632196)
Cold Spring Harb Perspect Biol. 2014 Jun 02;6(6):. (PMID: 24890514)
Curr Opin Immunol. 2006 Feb;18(1):39-48. (PMID: 16337366)
Oncol Rep. 2021 Jun;45(6):. (PMID: 33907853)
J Immunol. 2008 Aug 1;181(3):2220-6. (PMID: 18641362)
Sci Rep. 2019 Feb 28;9(1):3172. (PMID: 30816272)
Oncoimmunology. 2013 Dec 1;2(12):e26968. (PMID: 24498562)
Int Immunopharmacol. 2021 Aug;97:107823. (PMID: 34102486)
J Pathol. 2012 May;227(1):17-28. (PMID: 22262122)
Nature. 2012 Jul 18;487(7407):330-7. (PMID: 22810696)
Br J Cancer. 2007 Mar 26;96(6):986-92. (PMID: 17325702)
Int J Oncol. 2016 Oct;49(4):1297-304. (PMID: 27499237)
Cancer Res. 2014 Jan 1;74(1):153-161. (PMID: 24247719)
J Clin Invest. 2012 Mar;122(3):787-95. (PMID: 22378047)
Nature. 2017 Jan 18;541(7637):321-330. (PMID: 28102259)
Cancer Lett. 2021 Feb 1;498:111-120. (PMID: 33129954)
Cancer Cell. 2017 Mar 13;31(3):311-325. (PMID: 28292435)
Immunity. 2014 Jul 17;41(1):49-61. (PMID: 25035953)
Nature. 2013 Apr 25;496(7446):445-55. (PMID: 23619691)
J Leukoc Biol. 2017 Jan;101(1):285-295. (PMID: 27493241)
فهرسة مساهمة: Keywords: CSF-1R inhibitor; cancer-associated fibroblasts; colorectal cancer; pexidartinib; tumor-associated macrophages
المشرفين على المادة: 6783M2LV5X (pexidartinib)
0 (Immune Checkpoint Inhibitors)
0 (Aminopyridines)
0 (Pyrrolidines)
0 (Pyrroles)
تواريخ الأحداث: Date Created: 20240713 Date Completed: 20240713 Latest Revision: 20240715
رمز التحديث: 20240715
مُعرف محوري في PubMed: PMC11241126
DOI: 10.3390/ijms25137001
PMID: 39000110
قاعدة البيانات: MEDLINE
الوصف
تدمد:1422-0067
DOI:10.3390/ijms25137001