Cytolytic Activity (CYT) Score Is a Prognostic Biomarker Reflecting Host Immune Status in Hepatocellular Carcinoma (HCC)

Wakiyama, Hiroaki; Masuda, Takaaki; Motomura, Yuki; Hu, Qingjiang; Tobo, Taro; Eguchi, Hidetoshi; Sakamoto, Katsumi; Hirakawa, Masakazu; Honda, Hiroshi; Mimori, Koshi

doi:10.21873/anticanres.13030

Cited by 34 publications

(28 citation statements)

References 18 publications

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“…While these data suggest that the tumor immune dynamics in treated patients are notably different than in untreated patients, it may also simply reflect a very cancer or dataset specific sensitivity of the tumor fitness score. Indeed, as noted, the CYT measure alone seems to reduce survival prediction error, as found by others ( 21,22 ) and model authors themselves as a useful component to add to the tumor fitness score (3). Though the improvement of survival prediction by the inclusion of CYT may be, essentially, expected based on its efficacy as an independent predictor of therapy responsiveness in the checkpoint-setting (23), we demonstrate precisely in our work here this common-sense expectation to be true in the non-checkpoint setting as well.…”

Section: Discussionsupporting

confidence: 68%

Tumor fitness, immune exhaustion and clinical outcomes: impact of immune checkpoint inhibitors

Bubie

Gonzalez-Kozlova

Akers

et al. 2019

Preprint

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Recently proposed tumor fitness measures, based on profiling neoepitopes for reactive viral epitope similarity, have led to improved prediction models of response to immune checkpoint inhibitors in melanoma and small-cell lung cancer.Here we apply these checkpoint based fitness measures in the matched checkpoint-treatment naive TCGA samples where cytolytic activity imparts a known survival benefit. No significant survival predictive power beyond that of overall patient tumor mutational burden is observed in either cohort, and furthermore, there is no observed association between checkpoint based fitness and tumor T-cell infiltration, cytolytic activity (CYT), or abundance (TIL burden).We investigate the key assumption of viral epitope similarity driving immune response in the hepatitis B virally infected liver cancer TCGA cohort, and uncover suggestive evidence that tumor neoepitopes dominate viral epitopes in putative immunogenicity and plausibly drive immune response.Significance: Tumor fitness does not predict patient survival better than tumor mutation burden, unlike a measure of CYT. In checkpoint treatment naive patients, our results suggest TIL recruitment and cytolytic activity are essentially driven by tumor neoepitopes, regardless of the presence of viral epitopes.

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Section: Discussionsupporting

confidence: 68%

Tumor fitness, immune exhaustion and clinical outcomes: impact of immune checkpoint inhibitors

Bubie

Gonzalez-Kozlova

Akers

et al. 2019

Preprint

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“…UM is considered to be an immunotherapy-resistant subtype of melanoma, and UM patients are frequently excluded from clinical trials of immunotherapies for metastatic melanoma [20,39,40]. Although higher cytotoxic expression patterns are associated with better anti-tumor response and better patient survival in many solid tumors [34,41,42], the prognostic effects of immune infiltration depend on the type of tumor, the location of the cells and the state of activation. In UM, high levels of immune cells are associated with poor prognostic factors, such as M3 and BAP1 mutation [15,17,43].…”

Section: Discussionmentioning

confidence: 99%

Immunological analyses reveal an immune subtype of uveal melanoma with a poor prognosis

Pan

Liu

Cui

et al. 2020

Aging

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Uveal melanoma is an aggressive intraocular malignancy that often exhibits low immunogenicity. Metastatic uveal melanoma samples frequently exhibit monosomy 3 or BAP1 deficiency. In this study, we used bioinformatic methods to investigate the immune infiltration of uveal melanoma samples in public datasets. We first performed Gene Set Enrichment/Variation Analyses to detect immunological pathways that are altered in tumors with monosomy 3 or BAP1 deficiency. We then conducted an unsupervised clustering analysis to identify distinct immunologic molecular subtypes of uveal melanoma. We used CIBERSORT and ESTIMATE with RNA-seq data from The Cancer Genome Atlas and the GSE22138 microarray dataset to determine the samplelevel immune subpopulations and immune scores of uveal melanoma samples. The Kaplan-Meier method and log-rank test were used to assess the prognostic value of particular immune cells and genes in uveal melanoma samples. Through these approaches, we discovered uveal melanoma-specific immunologic features, which may provide new insights into the tumor microenvironment and enhance the development of immunotherapies in the future.

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“…. Immunohistochemical analysis of KIF15 expression was performed with formalin-fixed paraffinembedded surgical sections (FFPE) obtained from patients with HCC, or a HCC cell line (HepG2) or healthy donor PBMC, as previously described (21,26). Primary rabbit polyclonal antibody against KIF15 (ab90735; Abcam) was used at a dilution of 1:200.…”

Section: Immunohistochemical Analysis (Ihc)mentioning

confidence: 99%

KIF15 Expression in Tumor-associated Monocytes Is a Prognostic Biomarker in Hepatocellular Carcinoma

Kitagawa

Masuda

Takahashi

et al. 2020

Cancer Genomics Proteomics

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Background/Aim: Kinesin family member 15 (KIF15) participates in the transport of macromolecules in essential cellular processes. In this study we evaluated the clinical relevance of KIF15 expression in hepatocellular carcinoma (HCC). Materials and Methods: Association between KIF15 expression and clinical outcomes in HCC patients was analyzed using three independent cohorts. Localization of KIF15 expression was assessed by immunohistochemical analysis. Co-culture experiments were performed using healthy donor peripheral blood mononuclear cells (PBMC) and HCC cell lines. Results: Immunohistochemical analysis showed that KIF15 was mainly expressed in inflammatory monocytes around cancer cells. Multivariate analysis indicated high KIF15 expression was an independent poor prognostic factor for survival. HCC cells with high expression of minichromosome maintenance protein 2 (MCM2) were located close to KIF15expressing inflammatory monocytes. The proliferation ability of HCC cells was increased by co-culture with PBMC. Conclusion: High KIF15 expression in inflammatory monocytes in tumor tissues may serve as a prognostic marker for poor outcome in HCC.

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Cytolytic Activity (CYT) Score Is a Prognostic Biomarker Reflecting Host Immune Status in Hepatocellular Carcinoma (HCC)

Abstract: Book Reviews: Recently published books and journals should be sent to the Editorial Office. Reviews will be published within 2-4 months. Articles in ANTICANCER RESEARCH are regularly indexed in all bibliographic services, including Current Contents (Life Sciences), Science

Cited by 34 publications

References 18 publications

Tumor fitness, immune exhaustion and clinical outcomes: impact of immune checkpoint inhibitors

Tumor fitness, immune exhaustion and clinical outcomes: impact of immune checkpoint inhibitors

Immunological analyses reveal an immune subtype of uveal melanoma with a poor prognosis

KIF15 Expression in Tumor-associated Monocytes Is a Prognostic Biomarker in Hepatocellular Carcinoma

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