CR5/CCL5 axis is linked to a poor outcome, and inhibition reduces metastasis in oral squamous cell carcinoma.
Humans
Animals
Mice
Maraviroc
/ pharmacology
Carcinoma, Squamous Cell
/ drug therapy
Squamous Cell Carcinoma of Head and Neck
Retrospective Studies
Cell Line, Tumor
Mouth Neoplasms
/ drug therapy
RNA, Small Interfering
/ metabolism
Head and Neck Neoplasms
Tumor Microenvironment
Chemokine CCL5
/ genetics
CCL5 chemokine
CCR5 receptor
Metastasis
Oral cancer
Prognosis
Survival
Journal
Journal of cancer research and clinical oncology
ISSN: 1432-1335
Titre abrégé: J Cancer Res Clin Oncol
Pays: Germany
ID NLM: 7902060
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
received:
19
07
2023
accepted:
21
09
2023
medline:
20
11
2023
pubmed:
13
10
2023
entrez:
13
10
2023
Statut:
ppublish
Résumé
The CCR5/CCL5 axis is essential for interactions between malignant cells and microenvironment components, promoting tumor progression in oral squamous cell carcinoma (OSCC). This study aims to evaluate the association of CCL5 and CCR5 with the behavior of oral cancer and assess the therapeutic potential of a CCR5 antagonist. A retrospective study to analyze CCR5 and CCL5 expression on paraffin-embedded tissues was performed. In cell lines, rhCCL5 was added to induce CCR5-related pathways, and Maraviroc and shRNA against CCR5 were used to neutralize the receptor. Finally, an in vivo murine orthotopic xenograft model of tongue cancer was used to evaluate Maraviroc as an oncologic therapy. After 15 days, the mice were killed, and the primary tumors and cervical lymph nodes were analyzed. The expression of CCR5 was associated with clinical stage and metastasis, and CCL5 was related to overall survival. Adding rhCCL5 induced cell proliferation, while shRNA and Maraviroc reduced it in a dose-dependent manner. Maraviroc treatment also increased apoptosis and modified cytoskeletal organization. In vivo, Maraviroc reduced neck metastasis. The effects of CCR5 antagonists in OSCC have been poorly studied, and this study reports in vitro and in vivo evidence for the effects of Maraviroc in OSCC. Our results suggest that the CCR5/CCL5 axis plays a role in oral cancer behavior, and that its inhibition is a promising new therapy alternative.
Identifiants
pubmed: 37831273
doi: 10.1007/s00432-023-05443-1
pii: 10.1007/s00432-023-05443-1
doi:
Substances chimiques
Maraviroc
MD6P741W8A
RNA, Small Interfering
0
CCL5 protein, human
0
Chemokine CCL5
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
17335-17346Subventions
Organisme : Agencia Nacional de Investigación y Desarrollo (ANID) de Chile: Fondecyt Regular
ID : 1190775
Organisme : ANID-Basal funding for Scientific and Technological Center of Excellence, IMPACT
ID : FB210024
Organisme : Agencia Nacional de Investigación y Desarrollo (ANID) de Chile: Fondecyt de Iniciación
ID : 11180531
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
Références
Baba A, Okuyama Y, Ikeda K, Kozakai A, Suzuki T, Saito H, Ogane S, Yamazoe S, Yamauchi H, Ogino N, Seto Y, Kobashi Y, Mogami T, Ojiri H (2019) Undetectability of oral tongue cancer on magnetic resonance imaging; clinical significance as a predictor to avoid unnecessary elective neck dissection in node negative patients. Dentomaxillofac Radiol 48(3):20180272. https://doi.org/10.1259/dmfr.20180272
doi: 10.1259/dmfr.20180272
pubmed: 30608183
Bai S, Wu Y, Yan Y, Kang H, Zhang J, Ma W, Gao Y, Hui B, Zhang X, Ren J (2020) The effect of CCL5 on the immune cells infiltration and the prognosis of patients with kidney renal clear cell carcinoma. Int J Med Sci 17(18):2917–2925. https://doi.org/10.7150/ijms.51126
doi: 10.7150/ijms.51126
pubmed: 33173412
pmcid: 7646109
Borges GA, Elias ST, Amorim B, de Lima CL, Coletta RD, Castilho RM, Squarize CH, Silva EN (2020) Curcumin downregulates the PI3K-AKT-mTOR pathway and inhibits growth and progression in head and neck cancer cells. Phytother Res 34(12):3311–3324. https://doi.org/10.1002/ptr.6780
doi: 10.1002/ptr.6780
pubmed: 32628350
Cao Z, Xu X, Luo X, Li L, Huang B, Li X, Tao D, Hu J, Gong J (2011) Role of RANTES and its receptor in gastric cancer metastasis. J Huazhong Univ Sci Technolog Med Sci 31(3):342–347. https://doi.org/10.1007/s11596-011-0378-3
doi: 10.1007/s11596-011-0378-3
pubmed: 21671175
Capote-Moreno A, Brabyn P, Muñoz-Guerra MF, Sastre-Perez J, Escorial-Hernandez V, Rodríguez-Campo FJ, García T, Naval-Gías L (2020) Oral squamous cell carcinoma: epidemiological study and risk factor assessment based on a 39-year series. Int J Oral Maxillofac Surg 49(12):1525–1534. https://doi.org/10.1016/j.ijom.2020.03.009
doi: 10.1016/j.ijom.2020.03.009
pubmed: 32360101
Chen M, Yang X, Yang M, Zhang W, Li L, Sun Q (2019) Identification of a novel biomarker-CCL5 using antibody microarray for colorectal cancer. Pathol Res Pract 215(5):1033–1037. https://doi.org/10.1016/j.prp.2019.02.011
doi: 10.1016/j.prp.2019.02.011
pubmed: 30871911
Chuang JY, Yang WH, Chen HT, Huang CY, Tan TW, Lin YT, Hsu CJ, Fong YC, Tang CH (2009) CCL5/CCR5 axis promotes the motility of human oral cancer cells. J Cell Physiol 220(2):418–426. https://doi.org/10.1002/jcp.21783
doi: 10.1002/jcp.21783
pubmed: 19334035
da Silva JM, Soave DF, Moreira TP, Batista AC, Russo RC, Teixeira MM, da Silva TA (2016) Significance of chemokine and chemokine receptors in head and neck squamous cell carcinoma: a critical review. Oral Oncol 56:8–16. https://doi.org/10.1016/j.oraloncology.2016.02.016
doi: 10.1016/j.oraloncology.2016.02.016
pubmed: 27086481
Dantas TS, de Barros PG, Sousa EF, da Cunha MDP, de Aguiar ASW, Costa FWG, Mota MRL, Alves AP, Sousa FB (2016) Influence of educational level, stage, and histological type on survival of oral cancer in a Brazilian population: a retrospective study of 10 years observation. Med 95(3):e2314. https://doi.org/10.1097/MD.0000000000002314
doi: 10.1097/MD.0000000000002314
Deo SV, Shukla NK, Jha D, Khanna P, Pandit A, Thulkar S (2012) Are We over-treating neck in buccal & alveolo-buccal cancers: experience from a tertiary cancer care center. Indian J Surg Oncol 3(4):272–275. https://doi.org/10.1007/s13193-012-0173-z
doi: 10.1007/s13193-012-0173-z
pubmed: 24293960
pmcid: 3521543
Domingueti CB, Janini JBM, Paranaíba RLM, Lozano-Burgos C, Olivero P, González-Arriagada WA (2019) Prognostic value of immunoexpression of CCR4, CCR5, CCR7 and CXCR4 in squamous cell carcinoma of tongue and floor of the mouth. Med Oral Patol Oral Cir Bucal 24(3):e354–e363. https://doi.org/10.4317/medoral.22904
doi: 10.4317/medoral.22904
pubmed: 31011147
pmcid: 6530956
Dourado MR, Elseragy A, da Costa BC, Téo FH, Guimarães GN, Machado RA, Risteli M, Wahbi W, Gurgel CA, Ribeiro LM, González-Arriagada WA, da Silva SD, Carrinho AL, Rocha M, Rossa C, Salo T, Coletta RD (2022) Stress induced phosphoprotein 1 overexpression controls proliferation, migration and invasion and is associated with poor survival in oral squamous cell carcinoma. Front Oncol 12:1085917. https://doi.org/10.3389/fonc.2022.1085917
doi: 10.3389/fonc.2022.1085917
pubmed: 36713524
Gao T, Shen Z, Ma C, Li Y, Kang X, Sun M (2018) The CCL5/CCR5 chemotactic pathway promotes perineural invasion in salivary adenoid cystic carcinoma. J Oral Maxillofac Surg 76(8):1708–1718. https://doi.org/10.1016/j.joms.2018.02.009
doi: 10.1016/j.joms.2018.02.009
pubmed: 29549020
Gong R, Ren H (2020) Targeting chemokines/chemokine receptors: a promising strategy for enhancing the immunotherapy of pancreatic ductal adenocarcinoma. Signal Transduct Target Ther 5:149. https://doi.org/10.1038/s41392-020-00267-8
doi: 10.1038/s41392-020-00267-8
pubmed: 32782241
pmcid: 7419510
Gonzalez-Arriagada WA, Lozano-Burgos C, Zuniga-Moreta R, Gonzalez-Diaz P, Coletta RD (2018) Clinicopathological significance of chemokine receptor (CCR1, CCR3, CCR4, CCR5, CCR7 and CXCR4) expression in head and neck squamous cell carcinomas. J Oral Pathol Med 47(8):755–763. https://doi.org/10.1111/jop.12736
doi: 10.1111/jop.12736
pubmed: 29797610
Gonzalez-Arriagada WA, Garcia IE, Martinez-Flores R, Morales-Pison S, Coletta RD (2022) Therapeutic perspectives of HIV-associated chemokine receptor (CCR5 and CXCR4) antagonists in carcinomas. Int J Mol Sci 24(1):478. https://doi.org/10.3390/ijms24010478
doi: 10.3390/ijms24010478
pubmed: 36613922
pmcid: 9820365
Guan B, Li H, Yao J, Guo J, Yu F, Li G, Wan B, Ma J, Huang D, Sun L, Chen Y (2023) CCL3-CCR5 axis promotes cell migration and invasion of colon adenocarcinoma via Akt signaling pathway. Environ Toxicol 38(1):172–184. https://doi.org/10.1002/tox.23675
doi: 10.1002/tox.23675
pubmed: 36346222
Gulick RM, Fatkenheuer G, Burnside R, Hardy WD, Nelson MR, Goodrich J, Mukwaya G, Portsmouth S, Heera JR (2014) Five-year safety evaluation of maraviroc in HIV-1-infected treatment-experienced patients. J Acquir Immune Defic Syndr 65(1):78–81. https://doi.org/10.1097/QAI.0b013e3182a7a97a
doi: 10.1097/QAI.0b013e3182a7a97a
pubmed: 24419064
pmcid: 3893710
Haag GM, Springfeld C, Grün B, Apostolidis L, Zschäbitz S, Dietrich M, Berger AK, Weber TF, Zoernig I, Schaaf M, Waberer L, Müller DW, Al-Batran SE, Niels H, Jaeger D (2022) Pembrolizumab and maraviroc in refractory mismatch repair proficient/microsatellite-stable metastatic colorectal cancer—the PICCASSO phase I trial. Eur J Cancer 167:112–122. https://doi.org/10.1016/j.ejca.2022.03.017
doi: 10.1016/j.ejca.2022.03.017
pubmed: 35427833
Halvorsen EC, Hamilton MJ, Young A, Wadsworth BJ, LePard NE, Lee HN, Firmino N, Collier JL, Bennewith KL (2016) Maraviroc decreases CCL8-mediated migration of CCR5(+) regulatory T cells and reduces metastatic tumor growth in the lungs. Oncoimmunology 5(6):e1150398. https://doi.org/10.1080/2162402X.2016.1150398
doi: 10.1080/2162402X.2016.1150398
pubmed: 27471618
pmcid: 4938322
Hemmatazad H, Berger MD (2021) CCR5 is a potential therapeutic target for cancer. Expert Opin Ther Targets 25(4):311–327. https://doi.org/10.1080/14728222.2021.1902505
doi: 10.1080/14728222.2021.1902505
pubmed: 33719836
Huang H, Zepp M, Georges RB, Jarahian M, Kazemi M, Eyol E, Berger MR (2020) The CCR5 antagonist maraviroc causes remission of pancreatic cancer liver metastasis in nude rats based on cell cycle inhibition and apoptosis induction. Cancer Lett 474:82–93. https://doi.org/10.1016/j.canlet.2020.01.009
doi: 10.1016/j.canlet.2020.01.009
pubmed: 31954769
Huang R, Guo L, Gao M, Li J, Xiang S (2021) Research trends and regulation of CCL5 in prostate cancer. Onco Targets Ther 14:1417–1427. https://doi.org/10.2147/OTT.S279189
doi: 10.2147/OTT.S279189
pubmed: 33664576
pmcid: 7921632
Hunt PW, Shulman NS, Hayes TL, Dahl V, Somsouk M, Funderburg NT, McLaughlin B, Landay AL, Adeyemi O, Gilman LE, Clagett B, Rodriguez B, Martin JN, Schacker TW, Shacklett BL, Palmer S, Lederman MM, Deeks SG (2013) The immunologic effects of maraviroc intensification in treated HIV-infected individuals with incomplete CD4+ T-cell recovery: a randomized trial. Blood 121(23):4635–4646. https://doi.org/10.1182/blood-2012-06-436345
doi: 10.1182/blood-2012-06-436345
pubmed: 23589670
pmcid: 3685899
Jin K, Pandey NB, Popel AS (2018) Simultaneous blockade of IL-6 and CCL5 signaling for synergistic inhibition of triple-negative breast cancer growth and metastasis. Breast Cancer Res 20:54. https://doi.org/10.1186/s13058-018-0981-3
doi: 10.1186/s13058-018-0981-3
pubmed: 29898755
pmcid: 6000947
Kalpana G, Figy C, Yeung M, Yeung KC (2019) Reduced RhoA expression enhances breast cancer metastasis with a concomitant increase in CCR5 and CXCR4 chemokines signaling. Sci Rep 9:16351. https://doi.org/10.1038/s41598-019-52746-w
doi: 10.1038/s41598-019-52746-w
pubmed: 31705019
pmcid: 6841971
Kodama T, Koma YI, Arai N, Kido A, Urakawa N, Nishio M, Shigeoka M, Yokozaki H (2020) CCL3-CCR5 axis contributes to progression of esophageal squamous cell carcinoma by promoting cell migration and invasion via Akt and ERK pathways. Lab Invest 100:1140–1157. https://doi.org/10.1038/s41374-020-0441-4
doi: 10.1038/s41374-020-0441-4
pubmed: 32457351
pmcid: 7438203
Kolegova ES, Patysheva MR, Larionova IV, Fedorova IK, Kulbakin DE, Choinzonov EL, Denisov EV (2022) Early-onset oral cancer as a clinical entity: aetiology and pathogenesis. Int J Oral Maxillofac Surg 51(12):1497–1509. https://doi.org/10.1016/j.ijom.2022.04.005
doi: 10.1016/j.ijom.2022.04.005
pubmed: 35487818
Li C, Chen S, Liu C, Mo C, Gong W, Hu J, He M, Xie L, Hou X, Tang J, Ou M (2022a) CCR5 as a prognostic biomarker correlated with immune infiltrates in head and neck squamous cell carcinoma by bioinformatic study. Hereditas 159:37. https://doi.org/10.1186/s41065-022-00251-y
doi: 10.1186/s41065-022-00251-y
pubmed: 36167571
pmcid: 9513963
Li H, Wu M, Zhao X (2022b) Role of chemokine systems in cancer and inflammatory diseases. MedComm 3(2):e147. https://doi.org/10.1002/mco2.147
doi: 10.1002/mco2.147
pubmed: 35702353
pmcid: 9175564
Lin NC, Hsien SI, Hsu JT, Chen MYC (2020) Impact on patients with oral squamous cell carcinoma in different anatomical subsites: a single-center study in Taiwan. Sci Rep 11:15446. https://doi.org/10.1038/s41598-021-95007-5
doi: 10.1038/s41598-021-95007-5
Ling Z, Cheng B, Tao X (2021) Epithelial-to-mesenchymal transition in oral squamous cell carcinoma: challenges and opportunities. Int J Cancer 148(7):1548–1561. https://doi.org/10.1002/ijc.33352
doi: 10.1002/ijc.33352
pubmed: 33091960
Madera MV, Franco JV, Merchan-Galvis AM, Gallardo CR, Bonfill X (2018) Quality assessment of clinical practice guidelines on treatments for oral cancer. Cancer Treat Rev 65:47–53. https://doi.org/10.1016/j.ctrv.2018.03.001
doi: 10.1016/j.ctrv.2018.03.001
Manfroi B, De Grandis M, Moreaux J, Tabruyn S, Mayol JF, Quintero M, Righini C, Sturm N, Aurrand-Lions M, Huard B (2021) The microenvironment of DLBCL is characterized by noncanonical macrophages recruited by tumor-derived CCL5. Blood Adv 5(21):4338–4351. https://doi.org/10.1182/bloodadvances.2021004203
doi: 10.1182/bloodadvances.2021004203
pubmed: 34516642
pmcid: 8579261
Mencarelli A, Graziosi L, Renga B, Cipriani S, D’Amore C, Francisci D, Bruno A, Baldelli F, Donini A, Fiorucci S (2013) CCR5 antagonism by maraviroc reduces the potential for gastric cancer cell dissemination. Transl Oncol 6(6):784–793. https://doi.org/10.1593/tlo.13499
doi: 10.1593/tlo.13499
pubmed: 24466382
pmcid: 3890714
Neckel N, Michael M, Troeltzsch D, Wüster J, Koerdt S, Doll C, Jöhrens K, Neumann K, Heiland M, Raguse JD (2020) Rediscussing the role of traditional risk factors in young adults with oral squamous cell carcinoma. Anticancer Res 40(12):6987–6995. https://doi.org/10.21873/anticanres.14723
doi: 10.21873/anticanres.14723
pubmed: 33288593
Onyeisi JOS, Pernambuco PCA, Mesquita APS, Azevedo LC, Nader HB, Lopes CC (2020) Effects of syndecan-4 gene silencing by micro RNA interference in anoikis resistant endothelial cells: Syndecan-4 silencing and anoikis resistance. Int J Biochem Cell Biol 128:105848. https://doi.org/10.1016/j.biocel.2020.105848
doi: 10.1016/j.biocel.2020.105848
pubmed: 32927086
Pervaiz A, Ansari S, Berger MR, Adwan H (2015) CCR5 blockage by maraviroc induces cytotoxic and apoptotic effects in colorectal cancer cells. Med Oncol 32(5):158. https://doi.org/10.1007/s12032-015-0607-x
doi: 10.1007/s12032-015-0607-x
pubmed: 25840792
Pervaiz A, Zepp M, Mahmood S, Ali DM, Berger MR, Adwan H (2019) CCR5 blockage by maraviroc: a potential therapeutic option for metastatic breast cancer. Cell Oncol (dordr) 42(1):93–106. https://doi.org/10.1007/s13402-018-0415-3
doi: 10.1007/s13402-018-0415-3
pubmed: 30456574
Piconi S, Foschi A, Malagoli A, Carli F, Zona S, Milic J, Ricci ED, Rizzardini G, Guaraldi G (2019) Impact of prolonged maraviroc treatment on non-AIDS-related comorbidities in HIV-positive patients: a retrospective cohort study. J Antimicrob Chemother 74(9):2723–2731. https://doi.org/10.1093/jac/dkz227
doi: 10.1093/jac/dkz227
pubmed: 31139818
Qiu J, Xu L, Zeng X, Wu H, Liang F, Lv Q, Du Z (2022) CCL5 mediates breast cancer metastasis and prognosis through CCR5/Treg cells. Front Oncol 12:972383. https://doi.org/10.3389/fonc.2022.972383
doi: 10.3389/fonc.2022.972383
pubmed: 36033472
pmcid: 9399502
Satgunaseelan L, Allanson BM, Asher R, Reddy R, Low HTH, Veness M, Iyer NG, Smee RI, Palme CE, Gupta R, Clark JR (2020) The incidence of squamous cell carcinoma of the oral tongue is rising in young non-smoking women: an international multi-institutional analysis. Oral Oncol 110:104875. https://doi.org/10.1016/j.oraloncology.2020.104875
doi: 10.1016/j.oraloncology.2020.104875
pubmed: 32622292
Singh SK, Mishra MK, Eltoum IA, Bae S, Lillard JW Jr, Singh R (2018) CCR5/CCL5 axis interaction promotes migratory and invasiveness of pancreatic cancer cells. Sci Rep 8(1):1323. https://doi.org/10.1038/s41598-018-19643-0
doi: 10.1038/s41598-018-19643-0
pubmed: 29358632
pmcid: 5778036
Singh SK, Mishra MK, Rivers BM, Gordetsky JB, Bae S, Singh R (2020) Biological and clinical significance of the CCR5/CCL5 axis in hepatocellular carcinoma. Cancers (basel) 12(4):883. https://doi.org/10.3390/cancers12040883
doi: 10.3390/cancers12040883
pubmed: 32260550
Sobral LM, Bufalino A, Lopes MA, Graner E, Salo T, Coletta RD (2011) Myofibroblasts in the stroma of oral cancer promote tumorigenesis via secretion of activin A. Oral Oncol 47(9):840–846. https://doi.org/10.1016/j.oraloncology.2011.06.011
doi: 10.1016/j.oraloncology.2011.06.011
pubmed: 21727023
Somaida A, Tariq I, Ambreen G, Abdelsalam AM, Ayoub AM, Wojcik M, Dzoyem JP, Bakowsky U (2020) Potent cytotoxicity of four cameroonian plant extracts on different cancer cell lines. Pharm 13(11):357. https://doi.org/10.3390/ph13110357
doi: 10.3390/ph13110357
Stepan KO, Mazul AL, Larson J, Shah P, Jackson RS, Pipkorn P, Kang SY, Puram SV (2023) Changing epidemiology of oral cavity cancer in the United States. Otolaryngol Head Neck Surg 168(4):761–768. https://doi.org/10.1177/01945998221098011
doi: 10.1177/01945998221098011
pubmed: 35503657
Sugasawa H, Ichikura T, Tsujimoto H, Kinoshita M, Morita D, Ono S, Chochi K, Tsuda H, Seki S, Mochizuki H (2008) Prognostic significance of expression of CCL5/RANTES receptors in patients with gastric cancer. J Surg Oncol 97(5):445–450. https://doi.org/10.1002/jso.20984
doi: 10.1002/jso.20984
pubmed: 18297689
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F (2021) Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71(3):209–249. https://doi.org/10.3322/caac.21660
doi: 10.3322/caac.21660
pubmed: 33538338
Szturz P, Vermorken JB (2020) Management of recurrent and metastatic oral cavity cancer: raising the bar a step higher. Oral Oncol 101:104492. https://doi.org/10.1016/j.oraloncology.2019.104492
doi: 10.1016/j.oraloncology.2019.104492
pubmed: 31837576
Ucuncu M, Serilmez M, Sari M, Bademler S, Karabulut S (2019) The diagnostic significance of PDGF, EphA7, CCR5, and CCL5 levels in colorectal cancer. Biomol 9(9):464. https://doi.org/10.3390/biom9090464
doi: 10.3390/biom9090464
Velasco-Velazquez M, Jiao X, De La Fuente M, Pestell TG, Ertel A, Lisanti MP, Pestell RG (2012) CCR5 antagonist blocks metastasis of basal breast cancer cells. Cancer Res 72(15):3839–3850. https://doi.org/10.1158/0008-5472.CAN-11-3917
doi: 10.1158/0008-5472.CAN-11-3917
pubmed: 22637726
Wang T, Wei Y, Tian L, Song H, Ma Y, Yao Q, Feng M, Wang Y, Gao M, Xue Y (2016) C-C motif chemokine ligand 5 (CCL5) levels in gastric cancer patient sera predict occult peritoneal metastasis and a poorer prognosis. Int J Surg 32:136–142. https://doi.org/10.1016/j.ijsu.2016.07.008
doi: 10.1016/j.ijsu.2016.07.008
pubmed: 27398691
Wang L, Li L, Zhu G (2021) Role of extracellular vesicles on cancer lymphangiogenesis and lymph node metastasis. Front Oncol 11:721785. https://doi.org/10.3389/fonc.2021.721785
doi: 10.3389/fonc.2021.721785
pubmed: 34552874
pmcid: 8451414
Wang F, Tao Z, Tian Z, Jin J, Dong J, Dai Y, Yu W, Tang B, Hu S (2022) CCR5 as a prognostic factor in lower-grade glioma is involved in the remodeling of the tumor microenvironment. Front Genet 13:874896. https://doi.org/10.3389/fgene.2022.874896
doi: 10.3389/fgene.2022.874896
pubmed: 35865011
pmcid: 9294513
Weng CJ, Chien MH, Lin CW, Chung TT, Zavras AI, Tsai CM, Mk C, Yang SF (2010) Effect of CC chemokine ligand 5 and CC chemokine receptor 5 genes polymorphisms on the risk and clinicopathological development of oral cancer. Oral Oncol 46(10):767–772. https://doi.org/10.1016/j.oraloncology.2010.07.011
doi: 10.1016/j.oraloncology.2010.07.011
pubmed: 20729133
Willenbrock F, Cox CM, Parkes EE, Wilhelm-Benartzi CS, Abraham AG, Owens R, Sabbagh A, Jones CM, Hughes DLI, Maughan T, Hurt CN, O’Neill EE, Mukherjee S (2021) Circulating biomarkers and outcomes from a randomised phase 2 trial of gemcitabine versus capecitabine-based chemoradiotherapy for pancreatic cancer. Br J Cancer 124(3):581–586. https://doi.org/10.1038/s41416-020-01120-z
doi: 10.1038/s41416-020-01120-z
pubmed: 33100327
Xu L, Wu W, Cheng G, Qian M, Hu K, Yin G, Wang S (2017) Enhancement of proliferation and invasion of gastric cancer cell by KDM5C via decrease in p53 expression. Technol Cancer Res Treat 16(2):141–149. https://doi.org/10.1177/1533034616629261
doi: 10.1177/1533034616629261
pubmed: 26858085
Yang H, Son NH, Lee SH, Kim D, Kim HJ, Cha IH, Nam W (2021) Predictive modelling of level IIb lymph node metastasis in oral squamous cell carcinoma. Sci Rep 11(1):17562. https://doi.org/10.1038/s41598-021-96827-1
doi: 10.1038/s41598-021-96827-1
pubmed: 34475441
pmcid: 8413325
Zeng Z, Lan T, Wei Y, Wei X (2022) CCL5/CCR5 axis in human diseases and related treatments. Genes Dis 9(1):12–27. https://doi.org/10.1016/j.gendis.2021.08.004
doi: 10.1016/j.gendis.2021.08.004
pubmed: 34514075