Dynamic host immune response in virus-associated cancers

Cao, Song; Wylie, Kristine M.; Wyczalkowski, Matt A.; Karpova, Alla; Ley, Jessica; Sun, Sam Q.; Mashl, R. Jay; Liang, Wen Wei; Wang, Xiaowei; Johnson, Kimberly; DiPersio, John F.; Ratner, Lee; Chen, Feng; Adkins, Douglas R.; Li, Ding

doi:10.1038/s42003-019-0352-3

Cited by 35 publications

(30 citation statements)

References 71 publications

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“…The correlation of CD8 + T cell infiltration with overall survival in HPV-driven and in HPV-negative HNSCC demonstrated that independent of the HPV status, higher cytotoxic T cell infiltration is associated with increased overall survival (57, 59, 61). These results are in line with recent in silico studies analyzing The Cancer Genome Atlas (TCGA) data, that showed a higher level of T cell signatures in HPV-positive compared to virus-negative tumors (58, 63, 65–67), and especially that an immune response signature is associated with a favorable prognosis in patients with HPV-driven HNSCC (58, 63, 65, 66). Furthermore, Hess et al established an immune signature risk score (ISRS), based on the expression on 13 genes, robustly distinguishing patients with either a more favorable overall survival prognosis or a less favorable prognosis.…”

Section: Immune Responsessupporting

confidence: 90%

Enhanced Radiation Sensitivity of Human Papillomavirus-Driven Head and Neck Cancer: Focus on Immunological Aspects

2019

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Head and neck squamous cell carcinomas (HNSCC), emerging in the mucosa of the upper aerodigestive tract, are associated with either the classical risk factors, tobacco and alcohol consumption, or with infections with high-risk types of the human papillomavirus (HPV). Depending on the involvement of HPV, HNSCC follow different pathways of carcinogenesis and show distinct clinical presentations regarding survival, prognosis and treatment response. For instance, HPV-driven HNSCC exhibit an enhanced radiation response compared to their typically radioresistant HPV-negative counterparts. Although radiosensitivity of HNSCC has been studied by many research groups, the major causes for the difference in radiation responses between HPV-driven and HPV-negative HNSCC are still an open question. In this mini review, we discuss the reported cellular and immunological factors involved in the enhanced radiation response in HPV-driven HNSCC, focusing on the vital role of the immune response in the outcome of HNSCC radiotherapy.

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Section: Immune Responsessupporting

confidence: 90%

Enhanced Radiation Sensitivity of Human Papillomavirus-Driven Head and Neck Cancer: Focus on Immunological Aspects

2019

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“…Interestingly, the better outcomes seen in HPV + tumors may be partially related to their higher immune infiltration, as we observed. This may be explained by the highly immunogenic property of hrHPV, which could recruit immune effector cells, and upregulate the PD-1 and CTLA-4 immunosuppressive pathways [ 35 ]. Our findings also implicated mechanisms of T-cell escape in hrHPV + peSCC, wherein a high tumoral HPV-antigen load resulted in the high expression of PD-1 on T-cells.…”

Section: Discussionmentioning

confidence: 99%

Immunophenotypes Based on the Tumor Immune Microenvironment Allow for Unsupervised Penile Cancer Patient Stratification

Chu

Yao

et al. 2020

Cancers

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The tumor immune microenvironment (TIME) plays an important role in penile squamous cell carcinoma (peSCC) pathogenesis. Here, the immunophenotype of the TIME in peSCC was determined by integrating the expression patterns of immune checkpoints (programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1), cytotoxic T lymphocyte antigen 4 (CTLA-4), and Siglec-15) and the components of tumor-infiltrating lymphocytes, including CD8+ or Granzyme B+ T cells, FOXP3+ regulatory T cells, and CD68+ or CD206+ macrophages, in 178 patients. A high density of Granzyme B, FOXP3, CD68, CD206, PD-1, and CTLA-4 was associated with better disease-specific survival (DSS). The patients with diffuse PD-L1 tumor cell expression had worse prognoses than those with marginal or negative PD-L1 expression. Four immunophenotypes were identified by unsupervised clustering analysis, based on certain immune markers, which were associated with DSS and lymph node metastasis (LNM) in peSCC. There was no significant relationship between the immunophenotypes and high-risk human papillomavirus (hrHPV) infection. However, the hrHPV–positive peSCC exhibited a higher density of stromal Granzyme B and intratumoral PD-1 than the hrHPV–negative tumors (p = 0.049 and 0.002, respectively). In conclusion, the immunophenotypes of peSCC were of great value in predicting LNM and prognosis, and may provide support for clinical stratification management and immunotherapy intervention.

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“…It is urgent and critical to find inventive ways to predict response to ICI treatment. Accumulating evidences have documented the potential effects of HPV on HNSCC patients in several aspects including genomic integration, carcinogenesis, tumor angiogenesis, and TME (Troy et al, 2013;Parfenov et al, 2014;Cao et al, 2019;Wookey et al, 2019). Therefore, HPV status of HNSCC patients provides a promising entry point for predicting response to ICI therapy and unearthing the elusive molecular mechanism.…”

Section: Discussionmentioning

confidence: 99%

Systematic Profiling of Immune Risk Model to Predict Survival and Immunotherapy Response in Head and Neck Squamous Cell Carcinoma

Liu

Chen

et al. 2020

Front. Genet.

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Background and Purpose: Head and neck squamous carcinoma (HNSCC), characterized by immunosuppression, is a group of highly heterogeneous cancers. Although immunotherapy exerts a promising influence on HNSCC, the response rate remains low and varies in assorted primary sites. Immunological mechanisms underlying HNSCC pathogenesis and treatment response are not fully understood. This study aimed to develop a differentially expressed genes (DEGs)-based risk model to predict immunotherapy efficacy and stratify prognosis of HNSCC patients. Materials and Methods: The expression profiles of HNSCC patients were downloaded from The Cancer Genome Atlas (TCGA) database. The tumor microenvironment and immune response were estimated by cell type identification via estimating relative subset of known RNA transcripts (CIBERSORT) and immunophenoscore (IPS). The differential expression pattern based on human papillomavirus status was identified. A DEGsbased prognostic risk model was developed and validated. All statistical analyses were performed with R software (version 3.6.3). Results: By using the TCGA database, we identified DKK1, HBEGF, RNASE7, TNFRSF12A, INHBA, and IPIK3R3 as DEGs that were associated with patients' overall survival (OS). Patients were stratified into the high-and low-risk subgroups according to a DEGs-based prognostic risk model. Significant difference in OS was found between the high-and low-risk patients (1.64 vs. 2.18 years, P = 0.0017). In multivariate Cox analysis, the risk model was an independent prognostic factor for OS (hazard radio = 1.06, 95% confidence interval [1.02-1.10], P = 0.004). More CD8 + T cells and regulatory T cells were observed in the low-risk group and associated with a favorable prognosis. The IPS analysis suggested that the low-risk patients possessed a higher

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Dynamic host immune response in virus-associated cancers

Cited by 35 publications

References 71 publications

Enhanced Radiation Sensitivity of Human Papillomavirus-Driven Head and Neck Cancer: Focus on Immunological Aspects

Enhanced Radiation Sensitivity of Human Papillomavirus-Driven Head and Neck Cancer: Focus on Immunological Aspects

Immunophenotypes Based on the Tumor Immune Microenvironment Allow for Unsupervised Penile Cancer Patient Stratification

Systematic Profiling of Immune Risk Model to Predict Survival and Immunotherapy Response in Head and Neck Squamous Cell Carcinoma

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