Integrated immuno-transcriptomic analysis of ovarian cancer identifies a four-chemokine-dominated subtype with antitumor immune-active phenotype and favorable prognosis

Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023;73:17–48.Article 
PubMed 

Google Scholar 
Sun J, Bao S, Xu D, Zhang Y, Su J, Liu J, et al. Large-scale integrated analysis of ovarian cancer tumors and cell lines identifies an individualized gene expression signature for predicting response to platinum-based chemotherapy. Cell Death Dis. 2019;10:661.Article 
PubMed 
PubMed Central 

Google Scholar 
Chen L, Ma R, Luo C, Xie Q, Ning X, Sun K, et al. Noninvasive early differential diagnosis and progression monitoring of ovarian cancer using the copy number alterations of plasma cell-free DNA. Transl Res. 2023;262:12–24.Article 
CAS 
PubMed 

Google Scholar 
Veneziani AC, Gonzalez-Ochoa E, Alqaisi H, Madariaga A, Bhat G, Rouzbahman M, et al. Heterogeneity and treatment landscape of ovarian carcinoma. Nat Rev Clin Oncol. 2023;20:820–42.Article 
PubMed 

Google Scholar 
Yang Y, Wu SF, Bao W. Molecular subtypes of endometrial cancer: implications for adjuvant treatment strategies. Int J Gynaecol Obstet. 2024;164:436–59.Article 
CAS 
PubMed 

Google Scholar 
Guo CC, Lee S, Lee JG, Chen H, Zaleski M, Choi W, et al. Molecular profile of bladder cancer progression to clinically aggressive subtypes. Nat Rev Urol. 2024;21:391–405.Dienstmann R, Vermeulen L, Guinney J, Kopetz S, Tejpar S, Tabernero J. Consensus molecular subtypes and the evolution of precision medicine in colorectal cancer. Nat Rev Cancer. 2017;17:268.Article 
CAS 
PubMed 

Google Scholar 
Collisson EA, Bailey P, Chang DK, Biankin AV. Molecular subtypes of pancreatic cancer. Nat Rev Gastroenterol Hepatol. 2019;16:207–20.Article 
PubMed 

Google Scholar 
Yang Z, Zhang Y, Zhuo L, Sun K, Meng F, Zhou M, et al. Prediction of prognosis and treatment response in ovarian cancer patients from histopathology images using graph deep learning: a multicenter retrospective study. Eur J Cancer. 2024;199:113532.Article 
CAS 
PubMed 

Google Scholar 
Yang L, Zhang Z, Dong J, Zhang Y, Yang Z, Guo Y, et al. Multi-dimensional characterization of immunological profiles in small cell lung cancer uncovers clinically relevant immune subtypes with distinct prognoses and therapeutic vulnerabilities. Pharm Res. 2023;194:106844.Article 
CAS 

Google Scholar 
Thorsson V, Gibbs DL, Brown SD, Wolf D, Bortone DS, Ou Yang TH, et al. The immune landscape of cancer. Immunity. 2018;48:812–30 e14.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Engels CC, Fontein DB, Kuppen PJ, de Kruijf EM, Smit VT, Nortier JW, et al. Immunological subtypes in breast cancer are prognostic for invasive ductal but not for invasive lobular breast carcinoma. Br J Cancer. 2014;111:532–8.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Yan C, Li K, Meng F, Chen L, Zhao J, Zhang Z, et al. Integrated immunogenomic analysis of single-cell and bulk tissue transcriptome profiling unravels a macrophage activation paradigm associated with immunologically and clinically distinct behaviors in ovarian cancer. J Adv Res. 2023;44:149–60.Article 
CAS 
PubMed 

Google Scholar 
Sun J, Yan C, Xu D, Zhang Z, Li K, Li X, et al. Immuno-genomic characterisation of high-grade serous ovarian cancer reveals immune evasion mechanisms and identifies an immunological subtype with a favourable prognosis and improved therapeutic efficacy. Br J Cancer. 2022;126:1570–80.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Bertucci F, Niziers V, de Nonneville A, Finetti P, Mescam L, Mir O, et al. Immunologic constant of rejection signature is prognostic in soft-tissue sarcoma and refines the CINSARC signature. J Immunother Cancer. 2022;10:e003687.Article 
PubMed 
PubMed Central 

Google Scholar 
Teschendorff AE, Miremadi A, Pinder SE, Ellis IO, Caldas C. An immune response gene expression module identifies a good prognosis subtype in estrogen receptor negative breast cancer. Genome Biol. 2007;8:R157.Article 
PubMed 
PubMed Central 

Google Scholar 
Roelands J, Kuppen PJK, Ahmed EI, Mall R, Masoodi T, Singh P, et al. An integrated tumor, immune and microbiome atlas of colon cancer. Nat Med. 2023;29:1273–86.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Gautier L, Cope L, Bolstad BM, Irizarry RA. affy—analysis of affymetrix GeneChip data at the probe level. Bioinformatics. 2004;20:307–15.Article 
CAS 
PubMed 

Google Scholar 
Hao D, Li J, Jia S, Meng Y, Zhang C, Wang L, et al. Integrated analysis reveals tubal- and ovarian-originated serous ovarian cancer and predicts differential therapeutic responses. Clin Cancer Res. 2017;23:7400–11.Article 
CAS 
PubMed 

Google Scholar 
Mermel CH, Schumacher SE, Hill B, Meyerson ML, Beroukhim R, Getz G. GISTIC2.0 facilitates sensitive and confident localization of the targets of focal somatic copy-number alteration in human cancers. Genome Biol. 2011;12:R41.Article 
PubMed 
PubMed Central 

Google Scholar 
Markham A, Das R, Grosse-Wentrup M. A Distance Covariance-based Kernel for Nonlinear Causal Clustering in Heterogeneous Populations. In: Bernhard S, Caroline U, Kun Z, editors. Proceedings of the First Conference on Causal Learning and Reasoning; Proceedings of Machine Learning Research: PMLR; 2022. p. 542–58.Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA. 2005;102:15545–50.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Li B, Severson E, Pignon J-C, Zhao H, Li T, Novak J, et al. Comprehensive analyses of tumor immunity: implications for cancer immunotherapy. Genome Biol. 2016;17:174.Article 
PubMed 
PubMed Central 

Google Scholar 
Becht E, Giraldo NA, Lacroix L, Buttard B, Elarouci N, Petitprez F, et al. Estimating the population abundance of tissue-infiltrating immune and stromal cell populations using gene expression. Genome Biol. 2016;17:218.Article 
PubMed 
PubMed Central 

Google Scholar 
Barbie DA, Tamayo P, Boehm JS, Kim SY, Moody SE, Dunn IF, et al. Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1. Nature. 2009;462:108–12.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Racle J, de Jonge K, Baumgaertner P, Speiser DE, Gfeller D. Simultaneous enumeration of cancer and immune cell types from bulk tumor gene expression data. eLife. 2017;6:e26476.Zheng X, Wang X, Cheng X, Liu Z, Yin Y, Li X, et al. Single-cell analyses implicate ascites in remodeling the ecosystems of primary and metastatic tumors in ovarian cancer. Nat Cancer. 2023;4:1138–56.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Wang Y, Wang R, Zhang S, Song S, Wang L. iTALK: an R package to characterize and illustrate intercellular communication. Am Soc Hematol. 2019;Preprint at bioRxiv 507871.Humphries MP, Maxwell P, Salto-Tellez M. QuPath: The global impact of an open source digital pathology system. Computational Struct Biotechnol J. 2021;19:852–9.Article 
CAS 

Google Scholar 
Paschalis A, Sheehan B, Riisnaes R, Rodrigues DN, Gurel B, Bertan C, et al. Prostate-specific membrane antigen heterogeneity and DNA repair defects in prostate cancer. Eur Urol. 2019;76:469–78.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Bankhead P, Loughrey MB, Fernández JA, Dombrowski Y, McArt DG, Dunne PD, et al. QuPath: open source software for digital pathology image analysis. Sci Rep. 2017;7:16878.Article 
PubMed 
PubMed Central 

Google Scholar 
Roelands J, Hendrickx W, Zoppoli G, Mall R, Saad M, Halliwill K, et al. Oncogenic states dictate the prognostic and predictive connotations of intratumoral immune response. J Immunother Cancer. 2020;8:e000617.Article 
PubMed 
PubMed Central 

Google Scholar 
Bertucci F, Finetti P, Simeone I, Hendrickx W, Wang E, Marincola FM, et al. The immunologic constant of rejection classification refines the prognostic value of conventional prognostic signatures in breast cancer. Br J Cancer. 2018;119:1383–91.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Dillemans L, De Somer L, Neerinckx B, Proost P. A review of the pleiotropic actions of the IFN-inducible CXC chemokine receptor 3 ligands in the synovial microenvironment. Cell Mol Life Sci. 2023;80:78.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Mempel TR, Lill JK, Altenburger LM. How chemokines organize the tumour microenvironment. Nat Rev Cancer. 2024;24:28–50.Article 
CAS 
PubMed 

Google Scholar 
Romero JM, Grünwald B, Jang GH, Bavi PP, Jhaveri A, Masoomian M, et al. A four-chemokine signature is associated with a T-cell-inflamed phenotype in primary and metastatic pancreatic cancer. Clin Cancer Res. 2020;26:1997–2010.Article 
CAS 
PubMed 

Google Scholar 
Zha Y, Spranger S, Hernandez KM, Li Y, Bao R, Alexieff P, et al. Density of immunogenic antigens does not explain presence or absence of the T cell-inflamed tumor microenvironment in metastatic melanoma. J Immunother Cancer. 2015;3:1.Article 

Google Scholar 
K Au K, Peterson N, Truesdell P, Reid-Schachter G, Khalaj K, Ren R, et al. CXCL10 alters the tumour immune microenvironment and disease progression in a syngeneic murine model of high-grade serous ovarian cancer. Gynecol Oncol. 2017;145:436–45.Article 
PubMed 

Google Scholar 
Jin J, Li Y, Muluh TA, Zhi L, Zhao Q. Identification of CXCL10-relevant tumor microenvironment characterization and clinical outcome in ovarian cancer. Front Genet. 2021;12:678747.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Dangaj D, Bruand M, Grimm AJ, Ronet C, Barras D, Duttagupta PA, et al. Cooperation between constitutive and inducible chemokines enables T cell engraftment and immune attack in solid tumors. Cancer Cell. 2019;35:885–900.e10.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Peng D, Kryczek I, Nagarsheth N, Zhao L, Wei S, Wang W, et al. Epigenetic silencing of TH1-type chemokines shapes tumour immunity and immunotherapy. Nature. 2015;527:249–53.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Hoellwerth M, Koelblinger P, Lang R, Harrer A. Revisiting the role of the CXCL13/CXCR5-associated immune axis in melanoma: potential implications for Anti-PD-1-related biomarker research. Life. 2023;13:553.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Yang M, Lu J, Zhang G, Wang Y, He M, Xu Q, et al. CXCL13 shapes immunoactive tumor microenvironment and enhances the efficacy of PD-1 checkpoint blockade in high-grade serous ovarian cancer. J Immunother Cancer. 2021;9:e001136.Article 
PubMed 
PubMed Central 

Google Scholar 
Wylie B, Macri C, Mintern JD, Waithman J. Dendritic cells and cancer: from biology to therapeutic intervention. Cancers. 2019;11:521.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Xue J, Schmidt SV, Sander J, Draffehn A, Krebs W, Quester I, et al. Transcriptome-based network analysis reveals a spectrum model of human macrophage activation. Immunity. 2014;40:274–88.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Ostuni R, Kratochvill F, Murray PJ, Natoli G. Macrophages and cancer: from mechanisms to therapeutic implications. Trends Immunol. 2015;36:229–39.Article 
CAS 
PubMed 

Google Scholar 
Hensler M, Kasikova L, Fiser K, Rakova J, Skapa P, Laco J, et al. M2-like macrophages dictate clinically relevant immunosuppression in metastatic ovarian cancer. J Immunother Cancer. 2020;8:e000979.Article 
PubMed 
PubMed Central 

Google Scholar 

Hot Topics

Related Articles