Immunological Network in Head and Neck Squamous Cell Carcinoma—A Prognostic Tool Beyond HPV Status

Fialová, Alena; Koucký, Vladimír; Hajdůšková, Martina; Hladíková, Kamila; Špíšek, Radek

doi:10.3389/fonc.2020.01701

Cited by 19 publications

(16 citation statements)

References 145 publications

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“…This suggests that HPV-positive and HPV-negative tumor cells have different immune phenotypes. HPV-positive oropharyngeal tumors are characterized by a beneficial immune micro-environment with high levels of tumorinfiltrating lymphocytes [50]. Increased levels of both circulating and tumor infiltrating CD8+ T cells are related to better survival in HPV-positive HNSCC [51].…”

Section: Hypofractionated Rt Has a Bigger Influence On Cell Death Than Hpv Status In The Examined Four Hnscc Tumor Cell Linesmentioning

confidence: 99%

Hypofractionated Radiotherapy Upregulates Several Immune Checkpoint Molecules in Head and Neck Squamous Cell Carcinoma Cells Independently of the HPV Status While ICOS-L Is Upregulated Only on HPV-Positive Cells

Wimmer¹,

Deloch²,

Häder³

et al. 2021

IJMS

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While the treatment of squamous cell carcinoma of the head and neck (HNSCC) with radiotherapy (RT) is complemented more and more by immunotherapy in clinical trials, little is known about the impact of the human papillomavirus (HPV) status or the applied RT scheme on the immune phenotype of the tumor cells. Therefore, we aimed to examine the impact of the HPV status of four human HNSCC cell lines on cell death and the expression of immune checkpoint molecules (ICMs) after RT with either hypofractionation irradiation (5x3.0Gy) or a high single dose (1x19.3Gy) via multicolor flow cytometry and quantitative PCR at an early time point after therapy. In our study, 5x3.0Gy RT induced high numbers of early and late apoptotic cells independent of the HPV status, but necrosis was only increased in the HPV-positive UM-Scc-47 cells. Generally, the immune stimulatory ICMs (CD70, CD137-L, ICOS-L) were less affected by RT compared to the immune suppressive ones (PD-L1, PD-L2, and the herpesvirus entry mediator (HVEM)). A significant higher surface expression of the analyzed ICMs was found after hypofractionated RT compared to a single high dose; however, regardless of the HPV status, with the exception of ICOS-L. Here, HPV-positive HNSCC tumor cells showed a stronger response to 5x3.0Gy than HPV-negative ones. On the RNA level, only minor alterations of ICMs were observed following RT, with the exception of the HPV negative cell line CAL33 treated with 5x3.0Gy, where PD-L2, HVEM and CD70 were significantly increased. We conclude that the HPV status may not distinctly predict immunological responses following RT, and thus cannot be used as a single predictive marker for therapy responses in HNSCC. In contrast, the patient-specific individual expression of ICMs following RT is preferable for the targeted patient selection for immune therapy directed against distinct ICM.

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Section: Hypofractionated Rt Has a Bigger Influence On Cell Death Than Hpv Status In The Examined Four Hnscc Tumor Cell Linesmentioning

confidence: 99%

Hypofractionated Radiotherapy Upregulates Several Immune Checkpoint Molecules in Head and Neck Squamous Cell Carcinoma Cells Independently of the HPV Status While ICOS-L Is Upregulated Only on HPV-Positive Cells

Wimmer¹,

Deloch²,

Häder³

et al. 2021

IJMS

View full text Add to dashboard Cite

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“…By using a bioinformatic approach (CIBERSORT) that proved comparable to immunohistochemistry [ 27 ], we determined leukocyte infiltration levels. Tumors with a high RvD score evidenced increased CD4 + and CD8 + T cell infiltration, key for anti-tumor immunity in HNSC [ 39 , 40 ], but also decreased levels of anti-tumoral effectors such as plasma and dendritic cells, even if a specific subpopulation of these cells may also have a pro-tumorigenic role [ 41 ]. Therefore, increased activity of the RvD pathway significantly impacts on immune cell dynamics within the tumor microenvironment, likely due to alterations in cytokine/chemokine production ( Figure 3 D).…”

Section: Discussionmentioning

confidence: 99%

Gene Expression of the D-Series Resolvin Pathway Predicts Activation of Anti-Tumor Immunity and Clinical Outcomes in Head and Neck Cancer

Mattoscio

Ferri

Miccolo

et al. 2022

IJMS

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In human medicine, the progression from early neoplasia development to either complete resolution of tumorigenesis and associated inflammation or chronicity and fatal outcomes remain difficult to predict. Resolution of inflammation is an active process that stimulates the termination of the inflammatory response and promotes return to homeostasis, while failure in resolution contributes to the development of a number of diseases. To understand how resolution pathways contribute to tumorigenesis, we defined and employed a cumulative score based on the expression level of genes involved in synthesis, signaling, and metabolism of the D-series resolvin (RvD). This score was used for comparative analyses of clinical, cellular, and molecular features of tumors, based on RNA-sequencing (RNA-seq) datasets collected within The Cancer Genome Atlas (TCGA) program. Our results indicate that higher RvD scores are associated with better clinical outcome of patients with head and neck squamous cell carcinoma (HNSC), and with molecular and cellular signatures indicative of enhanced anti-tumor immunity and better response to immune-checkpoint inhibitors (ICI), also in human papilloma virus (HPV) negative HNSC subtypes. Thus, higher activity of the RvD pathway identifies patients with improved resolution and a more efficient immune reaction against cancer.

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“…One possible explanation may lie in the fact that HPV-positive OPSCC is actually a heterogeneous disease. Interestingly, a subgroup of patients with confirmed HPV-driven OPSCC were shown to have an immunologically “colder” microenvironment and markedly poorer clinical outcome ( 57 ). Given that PD-L1 is able to stratify the prognosis in the group of HPV-positive tumors, it could be interesting to explore the opportunity of using PD-L1, possibly together with other clinical and molecular parameters, as a tool to improve the selection of patients for treatment de-intensification trials.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Significance of PD-L1 Expression In Patients With Primary Oropharyngeal Squamous Cell Carcinoma: A Meta-Analysis

et al. 2021

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BackgroundAt present, the prognostic significance of programmed cell death receptor ligand 1 (PD-L1) expression in oropharyngeal squamous cell carcinoma (OPSCC) patients is still controversial. In this study, we aim to synthesize relevant studies that have assessed the prognostic value of PD-L1 in patients with primary OPSCC treated according to the current standard-of-care.MethodsA systematic search of Medline/PubMed, Cochrane, Embase, Web of Science, and Scopus was conducted to define the prognostic role of PD-L1 expression in OPSCC. All studies published before July 31, 2021 were screened. Summary hazard ratios (sHR) with 95% confidence intervals (CIs) were calculated using a random-effects model.ResultsA total of 1522 OPSCC patients from 12 studies were included. PD-L1 expression in OPSCC tumor cells (TCs) was significantly associated with longer overall survival (sHR=0.63, 95% CI 0.50-0.79), and progression-free survival (sHR=0.62, 95% CI 0.49-0.79). A benefit in survival was also observed in PD-L1-positive OPSCC patients who underwent surgery (sHR=0.34, 95% CI 0.18-0.65). Finally, although PD-L1-positive expression was related to better outcomes both in HPV-negative and HPV-positive OPSCC, the difference reached the statistical significance only in the HPV-positive subgroup (sHR=0.37, 95% CI 0.19-0.73). No heterogeneity emerged between studies for all considered outcomes, with I2 ranging from 0% for progression-free survival to 11% for overall survival.ConclusionsPD-L1 expression on TCs associated with improved survival in OPSCC. In particular, HPV-positive OPSCC most benefited from PD-L1 expression when compared to the PD-L1 negative counterpart. Thus, PD-L1 might represent a useful biomarker to stratify prognosis in OPSCC in addition to HPV status.

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Immunological Network in Head and Neck Squamous Cell Carcinoma—A Prognostic Tool Beyond HPV Status

Cited by 19 publications

References 145 publications

Hypofractionated Radiotherapy Upregulates Several Immune Checkpoint Molecules in Head and Neck Squamous Cell Carcinoma Cells Independently of the HPV Status While ICOS-L Is Upregulated Only on HPV-Positive Cells

Hypofractionated Radiotherapy Upregulates Several Immune Checkpoint Molecules in Head and Neck Squamous Cell Carcinoma Cells Independently of the HPV Status While ICOS-L Is Upregulated Only on HPV-Positive Cells

Gene Expression of the D-Series Resolvin Pathway Predicts Activation of Anti-Tumor Immunity and Clinical Outcomes in Head and Neck Cancer

Prognostic Significance of PD-L1 Expression In Patients With Primary Oropharyngeal Squamous Cell Carcinoma: A Meta-Analysis

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