{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T23:14:36Z","timestamp":1789600476144,"version":"build-2803163510"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2024,3,30]],"date-time":"2024-03-30T00:00:00Z","timestamp":1711756800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,3,30]],"date-time":"2024-03-30T00:00:00Z","timestamp":1711756800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81860720"],"award-info":[{"award-number":["81860720"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81860720"],"award-info":[{"award-number":["81860720"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81860720"],"award-info":[{"award-number":["81860720"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81860720"],"award-info":[{"award-number":["81860720"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81860720"],"award-info":[{"award-number":["81860720"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Project of Key Laboratory of Traditional Chinese Medicine in Jiangxi Province"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cancer Immunol Immunother"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Macrophage polarization is closely associated with the inflammatory processes involved in the development and chemoresistance of colorectal cancer (CRC). M2 macrophages, the predominant subtype of tumor-associated macrophages (TAMs) in a wide variety of malignancies, have been demonstrated to promote the resistance of CRC to multiple chemotherapeutic drugs, such as 5-fluorouracil (5-FU). In our study, we investigated the potential of 23-Hydroxybetulinic Acid (23-HBA), a significant active component of <jats:italic>Pulsatilla chinensis<\/jats:italic>\u00a0(<jats:italic>P. chinensis<\/jats:italic>), to inhibit the polarization of M2 macrophages induced by IL-4. Our results showed that 23-HBA reduced the expression of M2 specific marker CD206, while downregulating the mRNA levels of M2 related genes (CD206, Arg1, IL-10, and CCL2). Additionally, 23-HBA effectively attenuated the inhibitory effects of the conditioned medium from M2 macrophages on apoptosis in colorectal cancer SW480 cells. Mechanistically, 23-HBA prevented the phosphorylation and nuclear translocation of the STAT6 protein, resulting in the inhibition of IL-10 release in M2 macrophages. Moreover, it interfered with the activation of the IL-10\/STAT3\/Bcl-2 signaling pathway in SW480 cells, ultimately reducing M2 macrophage-induced resistance to 5-FU. Importantly, depleting STAT6 expression in macrophages abolished the suppressive effect of 23-HBA on M2 macrophage polarization, while also eliminating its ability to decrease M2 macrophage-induced 5-FU resistance in cancer cells. Furthermore, 23-HBA significantly diminished the proportion of M2 macrophages in the tumor tissues of colorectal cancer mice, simultaneously enhancing the anti-cancer efficacy of 5-FU. The findings presented in this study highlight the capacity of 23-HBA to inhibit M2 macrophage polarization, a process that contributes to reduced 5-FU resistance in colorectal cancer.<\/jats:p>","DOI":"10.1007\/s00262-024-03662-0","type":"journal-article","created":{"date-parts":[[2024,3,30]],"date-time":"2024-03-30T05:01:56Z","timestamp":1711774916000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["23-Hydroxybetulinic acid attenuates 5-fluorouracil resistance of colorectal cancer by modulating M2 macrophage polarization via STAT6 signaling"],"prefix":"10.1007","volume":"73","author":[{"given":"Zeping","family":"Fan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaru","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanying","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbin","family":"Duan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,30]]},"reference":[{"issue":"3","key":"3662_CR1","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung H, Ferlay J, Siegel RL et al (2021) Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71(3):209\u2013249. https:\/\/doi.org\/10.3322\/caac.21660","journal-title":"CA Cancer J Clin"},{"key":"3662_CR2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2019.107447","volume":"206","author":"S Vodenkova","year":"2020","unstructured":"Vodenkova S, Buchler T, Cervena K et al (2020) 5-fluorouracil and other fluoropyrimidines in colorectal cancer: past, present and future. Pharmacol Ther 206:107447. https:\/\/doi.org\/10.1016\/j.pharmthera.2019.107447","journal-title":"Pharmacol Ther"},{"key":"3662_CR3","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2020.100715","volume":"53","author":"N Erin","year":"2020","unstructured":"Erin N, Grahovac J, Brozovic A et al (2020) Tumor microenvironment and epithelial mesenchymal transition as targets to overcome tumor multidrug resistance. Drug Resist Update 53:100715. https:\/\/doi.org\/10.1016\/j.drup.2020.100715","journal-title":"Drug Resist Update"},{"key":"3662_CR4","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.656364","volume":"12","author":"K Khalaf","year":"2021","unstructured":"Khalaf K, Hana D, Chou JT et al (2021) Aspects of the tumor microenvironment involved in immune resistance and drug resistance. Front Immunol 12:656364. https:\/\/doi.org\/10.3389\/fimmu.2021.656364","journal-title":"Front Immunol"},{"key":"3662_CR5","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2020.107753","volume":"221","author":"Y Xiao","year":"2021","unstructured":"Xiao Y, Yu D (2021) Tumor microenvironment as a therapeutic target in cancer. Pharmacol Ther 221:107753. https:\/\/doi.org\/10.1016\/j.pharmthera.2020.107753","journal-title":"Pharmacol Ther"},{"issue":"6","key":"3662_CR6","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2023.188997","volume":"187","author":"Z Li","year":"2023","unstructured":"Li Z, Yin P (2023) Tumor microenvironment diversity and plasticity in cancer multidrug resistance. Biochim Biophys Acta Rev Cancer 187(6):188997. https:\/\/doi.org\/10.1016\/j.bbcan.2023.188997","journal-title":"Biochim Biophys Acta Rev Cancer"},{"issue":"1","key":"3662_CR7","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1186\/s40164-021-00252-z","volume":"10","author":"S Zhu","year":"2021","unstructured":"Zhu S, Yi M, Wu Y et al (2021) Roles of tumor-associated macrophages in tumor progression: implications on therapeutic strategies. Exp Hematol Oncol 10(1):60. https:\/\/doi.org\/10.1186\/s40164-021-00252-z","journal-title":"Exp Hematol Oncol"},{"issue":"1","key":"3662_CR8","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1038\/s41392-023-01452-1","volume":"8","author":"S Chen","year":"2023","unstructured":"Chen S, Saeed AFUH, Liu Q et al (2023) Macrophages in immunoregulation and therapeutics. Signal Transduct Target Ther 8(1):207. https:\/\/doi.org\/10.1038\/s41392-023-01452-1","journal-title":"Signal Transduct Target Ther"},{"issue":"1","key":"3662_CR9","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1038\/s41698-024-00522-z","volume":"8","author":"S Wang","year":"2024","unstructured":"Wang S, Wang J, Chen Z et al (2024) Targeting M2-like tumor-associated macrophages is a potential therapeutic approach to overcome antitumor drug resistance. NPJ Precis Oncol 8(1):31. https:\/\/doi.org\/10.1038\/s41698-024-00522-z","journal-title":"NPJ Precis Oncol"},{"key":"3662_CR10","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2023.101041","volume":"73","author":"H Wang","year":"2024","unstructured":"Wang H, Wang X, Zhang X et al (2024) The promising role of tumor-associated macrophages in the treatment of cancer. Drug Resist Update 73:101041. https:\/\/doi.org\/10.1016\/j.drup.2023.101041","journal-title":"Drug Resist Update"},{"key":"3662_CR11","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2022.215795","volume":"543","author":"TW Chen","year":"2022","unstructured":"Chen TW, Hung WZ, Chiang SF et al (2022) Dual inhibition of TGF\u03b2 signaling and CSF1\/CSF1R reprograms tumor-infiltrating macrophages and improves response to chemotherapy via suppressing PD-L1. Cancer Lett 543:215795. https:\/\/doi.org\/10.1016\/j.canlet.2022.215795","journal-title":"Cancer Lett"},{"key":"3662_CR12","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.113474","volume":"153","author":"YI Yang","year":"2022","unstructured":"Yang YI, Wang YY, Ahn JH et al (2022) CCL2 overexpression is associated with paclitaxel resistance in ovarian cancer cells via autocrine signaling and macrophage recruitment. Biomed Pharmacother 153:113474. https:\/\/doi.org\/10.1016\/j.biopha.2022.113474","journal-title":"Biomed Pharmacother"},{"issue":"3","key":"3662_CR13","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2023.04.023","volume":"11","author":"M Yu","year":"2023","unstructured":"Yu M, Wu Y, Li Q et al (2023) Colony-stimulating factor-1 receptor inhibition combined with paclitaxel exerts effective antitumor effects in the treatment of ovarian cancer. Genes Dis 11(3):100989. https:\/\/doi.org\/10.1016\/j.gendis.2023.04.023","journal-title":"Genes Dis"},{"key":"3662_CR14","doi-asserted-by":"publisher","first-page":"1274547","DOI":"10.3389\/fimmu.2023.1274547","volume":"14","author":"L Liu","year":"2023","unstructured":"Liu L, Chen G, Gong S et al (2023) Targeting tumor-associated macrophage: an adjuvant strategy for lung cancer therapy. Front Immunol 14:1274547. https:\/\/doi.org\/10.3389\/fimmu.2023.1274547","journal-title":"Front Immunol"},{"issue":"4","key":"3662_CR15","doi-asserted-by":"publisher","first-page":"1034","DOI":"10.1016\/j.ijrobp.2017.11.043","volume":"100","author":"OM Rahal","year":"2018","unstructured":"Rahal OM, Wolfe AR, Mandal PK et al (2018) Blocking interleukin (IL)4- and IL13-mediated phosphorylation of STAT6 (Tyr641) decreases M2 polarization of macrophages and protects against macrophage-mediated radioresistance of inflammatory breast cancer. Int J Radiat Oncol Biol Phys 100(4):1034\u20131043. https:\/\/doi.org\/10.1016\/j.ijrobp.2017.11.043","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"4","key":"3662_CR16","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1158\/2326-6066.CIR-22-0547","volume":"11","author":"K He","year":"2023","unstructured":"He K, Barsoumian HB, Puebla-Osorio N et al (2023) Inhibition of STAT6 with antisense oligonucleotides enhances the systemic antitumor effects of radiotherapy and anti-PD-1 in metastatic non-small cell lung cancer. Cancer Immunol Res 11(4):486\u2013500. https:\/\/doi.org\/10.1158\/2326-6066.CIR-22-0547","journal-title":"Cancer Immunol Res"},{"key":"3662_CR17","doi-asserted-by":"publisher","first-page":"1057181","DOI":"10.3389\/fimmu.2022.1057181","volume":"13","author":"G Cui","year":"2022","unstructured":"Cui G, Wang Z, Liu H et al (2022) Cytokine-mediated crosstalk between cancer stem cells and their inflammatory niche from the colorectal precancerous adenoma stage to the cancerous stage: mechanisms and clinical implications. Front Immunol 13:1057181. https:\/\/doi.org\/10.3389\/fimmu.2022.1057181","journal-title":"Front Immunol"},{"issue":"5","key":"3662_CR18","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1158\/2326-6066.Cir-16-0168","volume":"5","author":"SA Leon-Cabrera","year":"2017","unstructured":"Leon-Cabrera SA, Molina-Guzman E, Delgado-Ramirez YG et al (2017) Lack of STAT6 attenuates inflammation and drives protection against early steps of colitis-associated colon cancer. Cancer Immunol Res 5(5):385\u2013396. https:\/\/doi.org\/10.1158\/2326-6066.Cir-16-0168","journal-title":"Cancer Immunol Res"},{"issue":"6","key":"3662_CR19","doi-asserted-by":"publisher","first-page":"2130","DOI":"10.3390\/ijms21062130","volume":"21","author":"MG Mendoza-Rodr\u00edguez","year":"2020","unstructured":"Mendoza-Rodr\u00edguez MG, S\u00e1nchez-Barrera C, Callejas BE et al (2020) Use of STAT6 phosphorylation inhibitor and trimethylglycine as new adjuvant therapies for 5-fluorouracil in colitis-associated tumorigenesis. Int J Mol Sci 21(6):2130. https:\/\/doi.org\/10.3390\/ijms21062130","journal-title":"Int J Mol Sci"},{"issue":"3","key":"3662_CR20","doi-asserted-by":"publisher","first-page":"1112","DOI":"10.3390\/ijms23031112","volume":"23","author":"M Druszczy\u0144ska","year":"2022","unstructured":"Druszczy\u0144ska M, Godkowicz M, Kulesza J et al (2022) Cytokine receptors-regulators of antimycobacterial immune response. Int J Mol Sci 23(3):1112. https:\/\/doi.org\/10.3390\/ijms23031112","journal-title":"Int J Mol Sci"},{"key":"3662_CR21","doi-asserted-by":"publisher","first-page":"1026954","DOI":"10.3389\/fimmu.2022.1026954","volume":"13","author":"C Kerneur","year":"2022","unstructured":"Kerneur C, Cano CE, Olive D (2022) Major pathways involved in macrophage polarization in cancer. Front Immunol 13:1026954. https:\/\/doi.org\/10.3389\/fimmu.2022.1026954","journal-title":"Front Immunol"},{"issue":"5","key":"3662_CR22","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.349","volume":"4","author":"M Li","year":"2023","unstructured":"Li M, Wang M, Wen Y et al (2023) Signaling pathways in macrophages: molecular mechanisms and therapeutic targets. MedComm 4(5):e349. https:\/\/doi.org\/10.1002\/mco2.349","journal-title":"MedComm"},{"key":"3662_CR23","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1016\/j.ejmech.2017.12.039","volume":"144","author":"A Rejhov\u00e1","year":"2018","unstructured":"Rejhov\u00e1 A, Opattov\u00e1 A, \u010cumov\u00e1 A et al (2018) Natural compounds and combination therapy in colorectal cancer treatment. Eur J Med Chem 144:582\u2013594. https:\/\/doi.org\/10.1016\/j.ejmech.2017.12.039","journal-title":"Eur J Med Chem"},{"key":"3662_CR24","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2022.114445","volume":"188","author":"Q Gao","year":"2022","unstructured":"Gao Q, Feng J, Liu W et al (2022) Opportunities and challenges for co-delivery nanomedicines based on combination of phytochemicals with chemotherapeutic drugs in cancer treatment. Adv Drug Deliv Rev 188:114445. https:\/\/doi.org\/10.1016\/j.addr.2022.114445","journal-title":"Adv Drug Deliv Rev"},{"key":"3662_CR25","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2022.154431","volume":"107","author":"H Ma","year":"2022","unstructured":"Ma H, Zhou Z, Chen L et al (2022) Anemoside B4 prevents chronic obstructive pulmonary disease through alleviating cigarette smoke-induced inflammatory response and airway epithelial hyperplasia. Phytomedicine 107:154431. https:\/\/doi.org\/10.1016\/j.phymed.2022.154431","journal-title":"Phytomedicine"},{"key":"3662_CR26","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2020.105079","volume":"160","author":"Y Li","year":"2020","unstructured":"Li Y, Zou M, Han Q et al (2020) Therapeutic potential of triterpenoid saponin anemoside B4 from Pulsatilla chinensis. Pharmacol Res 160:105079. https:\/\/doi.org\/10.1016\/j.phrs.2020.105079","journal-title":"Pharmacol Res"},{"key":"3662_CR27","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.796745","volume":"12","author":"Z Liu","year":"2021","unstructured":"Liu Z, Wen X, Wang G et al (2021) Involvement of P-gp on reversing multidrug resistance effects of 23-hydroxybetulinic acid on chemotherapeutic agents. Front Pharmacol 12:796745. https:\/\/doi.org\/10.3389\/fphar.2021.796745","journal-title":"Front Pharmacol"},{"key":"3662_CR28","doi-asserted-by":"publisher","first-page":"1731457","DOI":"10.1155\/2020\/1731457","volume":"2020","author":"D Ngabire","year":"2020","unstructured":"Ngabire D, Niyonizigiye I, Patil MP et al (2020) M2 Macrophages mediate the resistance of gastric adenocarcinoma cells to 5-fluorouracil through the expression of integrin \u03b23, focal adhesion kinase, and cofilin. J Immunol Res 2020:1731457. https:\/\/doi.org\/10.1155\/2020\/1731457","journal-title":"J Immunol Res"},{"key":"3662_CR29","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.781233","volume":"12","author":"Y Li","year":"2022","unstructured":"Li Y, Chen Z, Han J et al (2022) Functional and therapeutic significance of tumor-associated macrophages in colorectal cancer. Front Oncol 12:781233. https:\/\/doi.org\/10.3389\/fonc.2022.781233","journal-title":"Front Oncol"},{"issue":"1","key":"3662_CR30","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1186\/s12916-022-02352-x","volume":"20","author":"C Huang","year":"2022","unstructured":"Huang C, Wang J, Liu H et al (2022) Ketone body \u03b2-hydroxybutyrate ameliorates colitis by promoting M2 macrophage polarization through the STAT6-dependent signaling pathway. BMC Med 20(1):148. https:\/\/doi.org\/10.1186\/s12916-022-02352-x","journal-title":"BMC Med"},{"key":"3662_CR31","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/j.freeradbiomed.2023.03.014","volume":"201","author":"Y Tu","year":"2023","unstructured":"Tu Y, Liu J, Kong D et al (2023) Irisin drives macrophage anti-inflammatory differentiation via JAK2-STAT6-dependent activation of PPAR\u03b3 and Nrf2 signaling. Free Radic Biol Med 201:98\u2013110. https:\/\/doi.org\/10.1016\/j.freeradbiomed.2023.03.014","journal-title":"Free Radic Biol Med"},{"key":"3662_CR32","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2021.108838","volume":"702","author":"Z He","year":"2021","unstructured":"He Z, Chen D, Wu J et al (2021) Yes associated protein 1 promotes resistance to 5-fluorouracil in gastric cancer by regulating GLUT3-dependent glycometabolism reprogramming of tumor-associated macrophages. Arch Biochem Biophys 702:108838. https:\/\/doi.org\/10.1016\/j.abb.2021.108838","journal-title":"Arch Biochem Biophys"},{"issue":"1","key":"3662_CR33","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1186\/s12935-022-02717-5","volume":"22","author":"P Su","year":"2022","unstructured":"Su P, Jiang L, Zhang Y et al (2022) Crosstalk between tumor-associated macrophages and tumor cells promotes chemoresistance via CXCL5\/PI3K\/AKT\/mTOR pathway in gastric cancer. Cancer Cell Int 22(1):290. https:\/\/doi.org\/10.1186\/s12935-022-02717-5","journal-title":"Cancer Cell Int"},{"issue":"9","key":"3662_CR34","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1038\/s41419-023-06108-0","volume":"14","author":"L Zhang","year":"2023","unstructured":"Zhang L, Lu X, Xu Y et al (2023) Tumor-associated macrophages confer colorectal cancer 5-fluorouracil resistance by promoting MRP1 membrane translocation via an intercellular CXCL17\/CXCL22-CCR4-ATF6-GRP78 axis. Cell Death Dis 14(9):582. https:\/\/doi.org\/10.1038\/s41419-023-06108-0","journal-title":"Cell Death Dis"},{"issue":"1","key":"3662_CR35","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1186\/s13045-017-0421-3","volume":"10","author":"Y Huang","year":"2017","unstructured":"Huang Y, Yang C, Wei P et al (2017) Ovatodiolide suppresses colon tumorigenesis and prevents polarization of M2 tumor-associated macrophages through YAP oncogenic pathways. J Hematol Oncol 10(1):60. https:\/\/doi.org\/10.1186\/s13045-017-0421-3","journal-title":"J Hematol Oncol"},{"issue":"5","key":"3662_CR36","doi-asserted-by":"publisher","first-page":"984","DOI":"10.7150\/ijbs.29836","volume":"15","author":"C Yang","year":"2019","unstructured":"Yang C, Wei C, Wang S et al (2019) Elevated CD163(+)\/CD68(+) ratio at tumor invasive front is closely associated with aggressive phenotype and poor prognosis in colorectal cancer. Int J Biol Sci 15(5):984\u2013998. https:\/\/doi.org\/10.7150\/ijbs.29836","journal-title":"Int J Biol Sci"},{"key":"3662_CR37","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2022.109569","volume":"116","author":"S Cheruku","year":"2023","unstructured":"Cheruku S, Rao V, Pandey R et al (2023) Tumor-associated macrophages employ immunoediting mechanisms in colorectal tumor progression: current research in macrophage repolarization immunotherapy. Int Immunopharmacol 116:109569. https:\/\/doi.org\/10.1016\/j.intimp.2022.109569","journal-title":"Int Immunopharmacol"},{"issue":"6","key":"3662_CR38","doi-asserted-by":"publisher","first-page":"1409","DOI":"10.1111\/bph.14816","volume":"177","author":"SR Lin","year":"2020","unstructured":"Lin SR, Chang CH, Hsu CF et al (2020) Natural compounds as potential adjuvants to cancer therapy: preclinical evidence. Br J Pharmacol 177(6):1409\u20131423. https:\/\/doi.org\/10.1111\/bph.14816","journal-title":"Br J Pharmacol"},{"key":"3662_CR39","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2022.154612","volume":"109","author":"Q Liu","year":"2023","unstructured":"Liu Q, Chen Y, An P et al (2023) Natural products targeting macrophages in tumor microenvironment are a source of potential antitumor agents. Phytomedicine 109:154612. https:\/\/doi.org\/10.1016\/j.phymed.2022.154612","journal-title":"Phytomedicine"},{"issue":"12","key":"3662_CR40","doi-asserted-by":"publisher","first-page":"1909","DOI":"10.1007\/s00262-019-02415-8","volume":"68","author":"Y Guo","year":"2019","unstructured":"Guo Y, Feng Y, Cui X et al (2019) Autophagy inhibition induces the repolarisation of tumour-associated macrophages and enhances chemosensitivity of laryngeal cancer cells to cisplatin in mice. Cancer Immunol Immunother 68(12):1909\u20131920. https:\/\/doi.org\/10.1007\/s00262-019-02415-8","journal-title":"Cancer Immunol Immunother"},{"key":"3662_CR41","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/j.canlet.2019.10.020","volume":"469","author":"Z Liu","year":"2020","unstructured":"Liu Z, Xie Y, Xiong Y et al (2020) TLR 7\/8 agonist reverses oxaliplatin resistance in colorectal cancer via directing the myeloid-derived suppressor cells to tumoricidal M1-macrophages. Cancer Lett 469:173\u2013185. https:\/\/doi.org\/10.1016\/j.canlet.2019.10.020","journal-title":"Cancer Lett"},{"issue":"4","key":"3662_CR42","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac","volume":"242","author":"X Zhan","year":"2023","unstructured":"Zhan X, Xu X, Zhang P et al (2023) Crude polysaccharide from Danggui Buxue decoction enhanced the anti-tumor effect of gemcitabine by remodeling tumor-associated macrophages. Int J Biol Macromol 242(4):125063. https:\/\/doi.org\/10.1016\/j.ijbiomac","journal-title":"Int J Biol Macromol"},{"key":"3662_CR43","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1016\/j.jconrel.2020.10.001","volume":"329","author":"F Emami","year":"2021","unstructured":"Emami F, Pathak S, Nguyen TT et al (2021) Photoimmunotherapy with cetuximab-conjugated gold nanorods reduces drug resistance in triple negative breast cancer spheroids with enhanced infiltration of tumor-associated macrophages. J Control Release 329:645\u2013664. https:\/\/doi.org\/10.1016\/j.jconrel.2020.10.001","journal-title":"J Control Release"}],"container-title":["Cancer Immunology, Immunotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00262-024-03662-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00262-024-03662-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00262-024-03662-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T18:03:42Z","timestamp":1713895422000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00262-024-03662-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,30]]},"references-count":43,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["3662"],"URL":"https:\/\/doi.org\/10.1007\/s00262-024-03662-0","relation":{},"ISSN":["1432-0851"],"issn-type":[{"value":"1432-0851","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,30]]},"assertion":[{"value":"1 January 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 February 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 March 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Animal studies was approved by the Institutional Animal Care & Use Committee of Jiangxi University of Traditional Chinese Medicine (identification code JZLLSC2023-0008).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}],"article-number":"83"}}