Down-regulation of stimulator of interferon genes (STING) expression and CD8
CD8+ T cells
HER2 heterogeneity
HER2-positive gastric cancer
STING signaling
Journal
Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association
ISSN: 1436-3305
Titre abrégé: Gastric Cancer
Pays: Japan
ID NLM: 100886238
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
received:
26
01
2023
accepted:
26
07
2023
medline:
13
11
2023
pubmed:
6
8
2023
entrez:
5
8
2023
Statut:
ppublish
Résumé
HER2 signaling might be involved in the regulation of immune cell activation in the tumor microenvironment (TME) of gastric cancer (GC). However, the relationship between HER2 status and immune cell condition in the HER2-positive GC TME is not clearly understood. To investigate the effect of HER2 signaling on the activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, which contributes to immune cell activation in the GC TME, we evaluated the associations among the expressions of HER2, cGAS-STING, and the number of CD8 The expression of HER2 is highly heterogeneous in HER2-positive GC tissues, and we found that the number of CD8 Our results suggest that HER2 signaling might suppress immune cell activation in the GC TME by inhibiting STING signaling in tumor cells in HER2-positive GC.
Sections du résumé
BACKGROUND
BACKGROUND
HER2 signaling might be involved in the regulation of immune cell activation in the tumor microenvironment (TME) of gastric cancer (GC). However, the relationship between HER2 status and immune cell condition in the HER2-positive GC TME is not clearly understood.
METHODS
METHODS
To investigate the effect of HER2 signaling on the activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, which contributes to immune cell activation in the GC TME, we evaluated the associations among the expressions of HER2, cGAS-STING, and the number of CD8
RESULTS
RESULTS
The expression of HER2 is highly heterogeneous in HER2-positive GC tissues, and we found that the number of CD8
CONCLUSIONS
CONCLUSIONS
Our results suggest that HER2 signaling might suppress immune cell activation in the GC TME by inhibiting STING signaling in tumor cells in HER2-positive GC.
Identifiants
pubmed: 37542528
doi: 10.1007/s10120-023-01417-x
pii: 10.1007/s10120-023-01417-x
doi:
Substances chimiques
Nucleotidyltransferases
EC 2.7.7.-
Interferons
9008-11-1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
878-890Subventions
Organisme : Japan Society for the Promotion of Science
ID : 22K08779
Organisme : Japan Society for the Promotion of Science
ID : 23K08177
Informations de copyright
© 2023. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.
Références
Smyth EC, Nilsson M, Grabsch HI, van Grieken NC, Lordick F. Gastric cancer. Lancet. 2020;396:635–48.
doi: 10.1016/S0140-6736(20)31288-5
pubmed: 32861308
Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022;72:7–33.
doi: 10.3322/caac.21708
pubmed: 35020204
Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol. 2001;2:127–37.
doi: 10.1038/35052073
pubmed: 11252954
Gravalos C, Jimeno A. HER2 in gastric cancer: a new prognostic factor and a novel therapeutic target. Ann Oncol. 2008;19:1523–9.
doi: 10.1093/annonc/mdn169
pubmed: 18441328
Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376:687–97.
doi: 10.1016/S0140-6736(10)61121-X
pubmed: 20728210
Janjigian YY, Kawazoe A, Yañez P, Li N, Lonardi S, Kolesnik O, et al. The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer. Nature. 2021;600:727–30.
doi: 10.1038/s41586-021-04161-3
pubmed: 34912120
pmcid: 8959470
Lv H, Zhang J, Sun K, Nie C, Chen B, Wang J, et al. Expression of human epidermal growth factor receptor-2 status and programmed cell death protein-1 ligand is associated with prognosis in gastric cancer. Front Oncol. 2020;10: 580045.
doi: 10.3389/fonc.2020.580045
pubmed: 33598422
Angell HK, Lee J, Kim KM, Kim K, Kim ST, Park SH, et al. PD-L1 and immune infiltrates are differentially expressed in distinct subgroups of gastric cancer. Oncoimmunology. 2018;8:e1544442.
doi: 10.1080/2162402X.2018.1544442
pubmed: 30729066
pmcid: 6351089
Cen S, Xu H, Liu Z, Zhao R, Pan H, Han W. Immune microenvironment characteristics and their implications for immune checkpoint inhibitor efficacy in HER2-overexpressing gastric cancer. Clin Exp Immunol. 2022;207:318–28.
doi: 10.1093/cei/uxac007
pubmed: 35553632
pmcid: 9113110
Valentini AM, Di Pinto F, Coletta S, Guerra V, Armentano R, Caruso ML. Tumor microenvironment immune types in gastric cancer are associated with mismatch repair however, not HER2 status. Oncol Lett. 2019;18:1775–85.
pubmed: 31423245
pmcid: 6614673
Suh KJ, Sung JH, Kim JW, Han SH, Lee HS, Min A, et al. EGFR or HER2 inhibition modulates the tumor microenvironment by suppression of PD-L1 and cytokines release. Oncotarget. 2017;8:63901–10.
doi: 10.18632/oncotarget.19194
pubmed: 28969039
pmcid: 5609971
Lian J, Zhang G, Zhang Y, Liu H, Zhang J, Nan P, et al. PD-L1 and HER2 expression in gastric adenocarcinoma and their prognostic significance. Dig Liver Dis. 2022;54:1419–27.
doi: 10.1016/j.dld.2022.01.128
pubmed: 35123909
Kurokawa Y, Matsuura N, Kimura Y, Adachi S, Fujita J, Imamura H, et al. Multicenter large-scale study of prognostic impact of HER2 expression in patients with resectable gastric cancer. Gastric Cancer. 2015;18:691–7.
doi: 10.1007/s10120-014-0430-7
pubmed: 25224659
Motoshima S, Yonemoto K, Kamei H, Morita M, Yamaguchi R. Prognostic implications of HER2 heterogeneity in gastric cancer. Oncotarget. 2018;9:9262–72.
doi: 10.18632/oncotarget.24265
pubmed: 29507688
pmcid: 5823644
Wakatsuki T, Yamamoto N, Sano T, Chin K, Kawachi H, Takahari D, et al. Clinical impact of intratumoral HER2 heterogeneity on trastuzumab efficacy in patients with HER2-positive gastric cancer. J Gastroenterol. 2018;53:1186–95.
doi: 10.1007/s00535-018-1464-0
pubmed: 29633013
pmcid: 6209002
Yagi S, Wakatsuki T, Yamamoto N, Chin K, Takahari D, Ogura M, et al. Clinical significance of intratumoral HER2 heterogeneity on trastuzumab efficacy using endoscopic biopsy specimens in patients with advanced HER2 positive gastric cancer. Gastric Cancer. 2019;22:518–25.
doi: 10.1007/s10120-018-0887-x
pubmed: 30328533
Ahn S, Ahn S, Van Vrancken M, Lee M, Ha SY, Lee H, et al. Ideal number of biopsy tumor fragments for predicting HER2 status in gastric carcinoma resection specimens. Oncotarget. 2015;6:38372–80.
doi: 10.18632/oncotarget.5368
pubmed: 26460823
pmcid: 4742006
Sokolowska O, Nowis D. STING signaling in cancer cells: important or not? Arch Immunol Ther Exp. 2018;66:125–32.
doi: 10.1007/s00005-017-0481-7
Gao M, He Y, Tang H, Chen X, Liu S, Tao Y. cGAS/STING: novel perspectives of the classic pathway. Mol Biomed. 2020;1:7.
doi: 10.1186/s43556-020-00006-z
pubmed: 35006429
pmcid: 8603984
Xia T, Konno H, Ahn J, Barber GN. Deregulation of STING signaling in colorectal carcinoma constrains DNA damage responses and correlates with tumorigenesis. Cell Rep. 2016;14:282–97.
doi: 10.1016/j.celrep.2015.12.029
pubmed: 26748708
Fuertes MB, Kacha AK, Kline J, Woo SR, Kranz DM, Murphy KM, et al. Host type I IFN signals are required for antitumor CD8+ T cell responses through CD8{alpha}+ dendritic cells. J Exp Med. 2011;208:2005–16.
doi: 10.1084/jem.20101159
pubmed: 21930765
pmcid: 3182064
Padovan E, Spagnoli GC, Ferrantini M, Heberer M. IFN-alpha2a induces IP-10/CXCL10 and MIG/CXCL9 production in monocyte-derived dendritic cells and enhances their capacity to attract and stimulate CD8+ effector T cells. J Leukoc Biol. 2002;71:669–76.
doi: 10.1189/jlb.71.4.669
pubmed: 11927654
An X, Zhu Y, Zheng T, Wang G, Zhang M, Li J, et al. An Analysis of the expression and association with immune cell infiltration of the cGAS/STING pathway in pan-cancer. Mol Ther Nucleic Acids. 2019;14:80–9.
doi: 10.1016/j.omtn.2018.11.003
pubmed: 30583098
Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity. 2013;39:1–10.
doi: 10.1016/j.immuni.2013.07.012
pubmed: 23890059
Song S, Peng P, Tang Z, Zhao J, Wu W, Li H, et al. Decreased expression of STING predicts poor prognosis in patients with gastric cancer. Sci Rep. 2017;7:39858.
doi: 10.1038/srep39858
pubmed: 28176788
pmcid: 5296877
Wu S, Zhang Q, Zhang F, Meng F, Liu S, Zhou R, et al. HER2 recruits AKT1 to disrupt STING signalling and suppress antiviral defence and antitumour immunity. Nat Cell Biol. 2019;21:1027–40.
doi: 10.1038/s41556-019-0352-z
pubmed: 31332347
Nakano H, Saito M, Nakajima S, Saito K, Nakayama Y, Kase K, et al. PD-L1 overexpression in EBV-positive gastric cancer is caused by unique genomic or epigenomic mechanisms. Sci Rep. 2021;11:1982.
doi: 10.1038/s41598-021-81667-w
pubmed: 33479394
pmcid: 7820576
Kikuchi T, Mimura K, Okayama H, Nakayama Y, Saito K, Yamada L, et al. A subset of patients with MSS/MSI-low-colorectal cancer showed increased CD8(+) TILs together with up-regulated IFN-γ. Oncol Lett. 2019;18:5977–85.
pubmed: 31788072
pmcid: 6865144
Gao J, Aksoy BA, Dogrusoz U, Dresdner G, Gross B, Sumer SO, et al. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal. 2013. https://doi.org/10.1126/scisignal.2004088 .
doi: 10.1126/scisignal.2004088
pubmed: 24170934
pmcid: 3969021
Davoli T, Uno H, Wooten EC, Elledge SJ. Tumor aneuploidy correlates with markers of immune evasion and with reduced response to immunotherapy. Science. 2017. https://doi.org/10.1126/science.aaf8399 .
doi: 10.1126/science.aaf8399
pubmed: 28104840
pmcid: 5592794
Jani JP, Finn RS, Campbell M, Coleman KG, Connell RD, Currier N, et al. Discovery and pharmacologic characterization of CP-724,714, a selective ErbB2 tyrosine kinase inhibitor. Cancer Res. 2007;67:9887–93.
doi: 10.1158/0008-5472.CAN-06-3559
pubmed: 17942920
Ozga AJ, Chow MT, Luster AD. Chemokines and the immune response to cancer. Immunity. 2021;54:859–74.
doi: 10.1016/j.immuni.2021.01.012
pubmed: 33838745
pmcid: 8434759
Hannesdóttir L, Tymoszuk P, Parajuli N, Wasmer MH, Philipp S, Daschil N, et al. Lapatinib and doxorubicin enhance the Stat1-dependent antitumor immune response. Eur J Immunol. 2013;43:2718–29.
doi: 10.1002/eji.201242505
pubmed: 23843024
Nakajima S, Mimura K, Matsumoto T, Thar Min AK, Ito M, Nakano H, et al. The effects of T-DXd on the expression of HLA class I and chemokines CXCL9/10/11 in HER2-overexpressing gastric cancer cells. Sci Rep. 2021;11:16891.
doi: 10.1038/s41598-021-96521-2
pubmed: 34413454
pmcid: 8376901
Harlin H, Meng Y, Peterson AC, Zha Y, Tretiakova M, Slingluff C, et al. Chemokine expression in melanoma metastases associated with CD8+ T-cell recruitment. Cancer Res. 2009;69:3077–85.
doi: 10.1158/0008-5472.CAN-08-2281
pubmed: 19293190
Ahn J, Konno H, Barber GN. Diverse roles of STING-dependent signaling on the development of cancer. Oncogene. 2015;34:5302–8.
doi: 10.1038/onc.2014.457
pubmed: 25639870
pmcid: 4998969
Ma F, Li B, Yu Y, Iyer SS, Sun M, Cheng G. Positive feedback regulation of type I interferon by the interferon-stimulated gene STING. EMBO Rep. 2015;16:202–12.
doi: 10.15252/embr.201439366
pubmed: 25572843
pmcid: 4328747
Chen HY, Pang XY, Xu YY, Zhou GP, Xu HG. Transcriptional regulation of human cyclic GMP-AMP synthase gene. Cell Signal. 2019;62: 109355.
doi: 10.1016/j.cellsig.2019.109355
pubmed: 31276766
Guarnieri F. Designing an orally available nontoxic p38 inhibitor with a fragment-based strategy. Methods Mol Biol. 2015;1289:211–26.
doi: 10.1007/978-1-4939-2486-8_15
pubmed: 25709042