Immune biomarkers of response to immune-checkpoint inhibitors in head and neck squamous cell carcinoma

Oliva, Marc; Spreafico, Anna; Cequier, Ángel; Alemany, Laia; Coburn, Bryan; Mesı́a, Ricard; Siu, Lillian L.

doi:10.1093/annonc/mdy507

Cited by 193 publications

(179 citation statements)

References 136 publications

(212 reference statements)

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“…Additionally, we also observed a positive association between the number of expressed CT genes with different types of immune cells. Recently, there is accumulating evidence confirming the association between immune biomarkers and the response to anti‐PD‐1/L1 therapy across several solid tumors . In this study, we found that PD‐1 / PD‐L1 expression was positively correlated with the number of expressed CT genes, suggesting that CT genes represent a potential marker for effective PD‐1/L1 immunotherapy.…”

Section: Discussionsupporting

confidence: 64%

Comprehensive characterization of cancer‐testis genes in testicular germ cell tumor

Chang

Wang

et al. 2019

Cancer Medicine

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Cancer‐testis (CT) genes are a group of genes restrictedly expressed in testis and multiple cancers and can serve as candidate driver genes participating in the development of cancers. Our previous study identified a number of CT genes in nongerm cell tumors, but their expression pattern in testicular germ cell tumor (TGCT), a cancer type characterized by less genomic alterations, remained largely unknown. In this study, we systematically investigated the expression pattern of CT genes in TGCT samples and evaluated the transcriptome difference between TGCT and normal testis tissues, using datasets from the UCSC Xena platform, The Cancer Genome Atlas (TCGA) and the Genotype‐Tissue Expression (GTEx) project. Pathway enrichment analysis and survival analysis were conducted to evaluate the biological function and prognostic effect of expressed CT genes. We identified that 1036 testis‐specific expressed protein‐coding genes and 863 testis‐specific expressed long noncoding RNAs (lncRNAs) were expressed in TGCT samples, including 883 CT protein‐coding genes and 710 CT lncRNAs defined previously. The number of expressed CT genes was significantly higher in seminomas ( P = 3.48 × 10 −13 ) which were characterized by frequent mutations in driver genes ( KIT , KRAS and NRAS ). In contrast, the number of expressed CT genes showed a moderate negative correlation with the fraction of copy number altered genomes (cor = −0.28, P = 1.20 × 10 −3 ). Unlike other cancers, our analysis revealed that 96.16% of the CT genes were down‐regulated in TGCT samples, while CT genes in stem cell maintenance related pathways were up‐regulated. Further survival analysis provided evidence that CT genes could also predict the prognosis of TGCT patients with both disease‐free interval and progression‐free interval as clinical endpoints. Taken together, our study provided a global view of CT genes in TGCT and provided evidence that CT genes played important roles in the progression and maintenance of TGCT.

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Section: Discussionsupporting

confidence: 64%

Comprehensive characterization of cancer‐testis genes in testicular germ cell tumor

Chang

Wang

et al. 2019

Cancer Medicine

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“…Given the small number of patients with uterine cervical cancer for whom HPV status could be determined (12 of 20 patients), it is difficult to evaluate the relationship between HPV status and response to nivolumab in the current study. Studies investigating the relationship between HPV status and response to nivolumab have had mixed results …”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of nivolumab in Japanese patients with uterine cervical cancer, uterine corpus cancer, or soft tissue sarcoma: Multicenter, open‐label phase 2 trial

Tamura¹,

Hasegawa

Katsumata

et al. 2019

Cancer Science

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Nivolumab is a human monoclonal antibody against the immune checkpoint receptor programmed death‐1, inhibiting binding to programmed death‐ligand 1 or 2 (PD‐L1 or PD‐L2). This phase 2 study evaluated the efficacy and safety of nivolumab in patients with advanced/recurrent uterine cervical cancer, uterine corpus cancer, or soft tissue sarcoma (STS). Patients received nivolumab 240 mg at 2‐week intervals. Primary endpoint was objective response rate; secondary endpoints included overall survival, progression‐free survival, and safety. PD‐L1 expression and microsatellite‐instability (MSI) status were analyzed as potential efficacy biomarkers. Objective response rate was 25%, 23%, and 0% in patients with cervical cancer (n = 20), corpus cancer (n = 22), and STS (n = 21), respectively. The lower 80% confidence intervals of objective response rates in patients with cervical or corpus cancer exceeded the threshold rate (5%); the primary endpoint was met in cervical and corpus cancer, but not in STS. Median progression‐free survival was 5.6, 3.4, and 1.4 months, and 6‐month overall survival was 84%, 73%, and 86% in cervical cancer, corpus cancer, and STS, respectively. The objective response rate was higher in patients with cervical cancer with PD‐L1‐positive (n = 5/15; 33%) versus PD‐L1‐negative (n = 0/5; 0%) tumors. The two patients with corpus cancer classified as MSI‐high responded; the six patients classified as microsatellite stable did not respond. Overall, nivolumab showed acceptable toxicity in all cohorts, with evidence of clinical activity in uterine cervical or corpus cancer, but not in STS. PD‐L1 expression in cervical cancer and MSI‐high in corpus cancer may predict clinical activity of nivolumab in these cancers.

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“…Ten members are included in the B7/CD28 family, including B7-1/CD28, B7-2/cytotoxic T lymphocyte antigen 4 (CTLA-4), ICOS-L/ICOS and programmed cell death 1 (PD-1)/PD-1 ligand (PD-L1). 8,9 Inhibitors of PD-L1/PD-1 have been approved by Food and Drug Administration (FDA) as second-line treatments for lung cancer, because of their therapeutic benefit in clinical trials. 6,7 The B7/CD28 family regulates the proliferation and function of T cells as antigen-presenting cells (APCs).…”

Section: Introductionmentioning

confidence: 99%

“…(range:[1][2][3][4][5][6][7][8][9][10][11][12]. The median score was used to determine the cut-off value of low or high CD28H expression.…”

mentioning

confidence: 99%

Overexpression of B7H5/CD28H is associated with worse survival in human gastric cancer

Chen

et al. 2019

J Cellular Molecular Medi

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Gastric cancer (GC) is a common malignancy with low 5-year overall survival (OS).Recently, immune therapy has been used to treat cancer. B7H5 and CD28H are novel immune checkpoint molecules. However, the prognostic value of B7H5/CD28H expression in patients with GC remains unclear. In this study, seventy-one patients diagnosed with GC were included in this study. Patients' GC tissues and matched adjacent tissue constructed a tissue microarray. The expression levels of B7H5 and CD28H were examined using immunohistochemistry. Correlations between the expression of B7H5 and CD28H and the clinical data were evaluated. We found that the expression of B7H5 and CD28H (both P = .001) were higher in GC tumour tissues than in adjacent noncancerous tissues. B7H5/CD28H expression acted as an independent predictive factor in the OS of patients with GC. High expression of B7H5 and CD28H predicted poor outcome.Patients in the B7H5+CD28H+ group had a lower 5-year OS compared with patients in the B7H5−CD28− group (4.5% vs 55.6%, P = .001). A significant difference was found in the 5-year OS between patients in the B7H5+CD28H− and B7H5+CD28H+ groups (33.5% vs 4.5%, P = .006). However, there was no correlation between B7H5 and CD28H expression (P = .844). Therefore, B7H5 and CD28H expression are up-regulated in GC and are independent prognostic factors for overall survival in patients with GC. Although there was no correlation between B7H5 and CD28H expression, high expression of B7H5 and CD28H predicts poor prognosis, especially when both are highly expressed. K E Y W O R D SB7 family checkpoints, B7H5, CD28H, gastric cancer, immunotherapy

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Immune biomarkers of response to immune-checkpoint inhibitors in head and neck squamous cell carcinoma

Cited by 193 publications

References 136 publications

Comprehensive characterization of cancer‐testis genes in testicular germ cell tumor

Comprehensive characterization of cancer‐testis genes in testicular germ cell tumor

Efficacy and safety of nivolumab in Japanese patients with uterine cervical cancer, uterine corpus cancer, or soft tissue sarcoma: Multicenter, open‐label phase 2 trial

Overexpression of B7H5/CD28H is associated with worse survival in human gastric cancer

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