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Cancers
Special Issues
The Tumor Microenvironment and Immunotherapy of Head and Neck Cancer
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The Tumor Microenvironment and Immunotherapy of Head and Neck Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Tumor Microenvironment".

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 5511

Special Issue Editor

Prof. Dr. Yu-Chao Chang

E-Mail Website
Guest Editor
College of Oral Medicine, Chung-Shan Medical University, Taiwan
Interests: head and neck cancer; tumor microenvironment; immunotherapy

Special Issue Information

Dear Colleagues,

Head and neck cancer (HNC) is one of the most common types of malignant tumor. HNC patients frequently experience and suffer from recurrence, metastasis, and poor prognosis. HNC clinical therapies mostly include surgical resection, radiotherapy, and chemotherapy. However, the biggest concerns with clinical therapy remain related to the tumor microenvironment (TME), which has an unfavorable impact on therapeutic outcomes. TME is a complex and heterogeneous mix of tumor cells and stromal cells, including endothelial cells, cancer-associated fibroblasts and immune cells. TME is also known to be closely related to the occurrence, growth, and metastasis of tumor. TMEs contribute to the establishment of an immunosuppressive network, which can lead to immune resistance and, ultimately, facilitate tumor growth or the metastasis of the tumor. Therefore, the key factors of tumor immune suppression include high levels of extracellular matrix, hypoxia, immunosuppressive cytokines, toxic metabolites, and high expression of immune checkpoint molecules. In recent years, immune checkpoint, adoptive cell transfer, cancer vaccine, and oncolytic virus treatments have all been used to treat cancer. However, due to TME heterogeneity, treatment responses in cancers are unpredictable even when the same immunotherapy is used. In HNC, HPV infection alters the TME of the immune cell landscape, resulting in HPV-positive HNC patients having a better prognosis compared to HPV-negative HNC patients. Considering that TME high heterogeneity leads to varying outcomes in immunotherapy patients, a deeper understanding of immune cells in the TME is essential for deciphering immunotherapies mechanisms, defining predictive biomarkers, and discovering novel therapeutic targets. The aim of this Special Issue is to collect original articles and reviews to better understand TME and the immunotherapy of HNC.

Prof. Dr. Yu-Chao Chang
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • head and neck cancer
  • tumor microenvironment
  • immunotherapy
  • immunotherapies mechanisms
  • predictive biomarkers
  • novel therapeutic targets

Published Papers (3 papers)

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Research

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15 pages, 3142 KiB  
Article
HPV-Negative and HPV-Positive Oral Cancer Cells Stimulate the Polarization of Neutrophils towards Different Functional Phenotypes In Vitro
by Marcela Guadalupe Martínez-Barajas, Luis Felipe Jave-Suárez, Inocencia Guadalupe Ramírez-López, Mariel García-Chagollán, José Sergio Zepeda-Nuño, Adrián Ramírez-de-Arellano, Pablo César Ortiz-Lazareno, Julio César Villegas-Pineda and Ana Laura Pereira-Suárez
Cancers 2023, 15(24), 5814; https://doi.org/10.3390/cancers15245814 - 12 Dec 2023
Cited by 1 | Viewed by 1784
Abstract
High-risk human papillomavirus (HPV) infection is one of the leading causes of oropharyngeal squamous cell carcinoma (OPSCC), while the correlation between HPV and oral squamous cell carcinoma (OSCC) remains controversial. The inflammatory infiltrate involved in these epithelial neoplasms differs based on their association [...] Read more.
High-risk human papillomavirus (HPV) infection is one of the leading causes of oropharyngeal squamous cell carcinoma (OPSCC), while the correlation between HPV and oral squamous cell carcinoma (OSCC) remains controversial. The inflammatory infiltrate involved in these epithelial neoplasms differs based on their association with HPV. HPV− tumors show higher tumor-associated neutrophil (TAN) infiltration. It is believed that TANs can play a dual role in cancer by exerting either anti-tumorigenic or pro-tumorigenic effects. However, the impact of HPV status on neutrophil polarization remains unknown. Therefore, this study aimed to investigate the effect of OSCC cells, both HPV− and HPV16+, on the functional phenotype of neutrophils. Peripheral blood neutrophils were stimulated with supernatants from OSCC cell lines and non-tumorigenic HaCaT keratinocytes transduced with HPV16 E6/E7 oncogenes. Subsequently, cytokine production, cell viability, metabolism, expression of degranulation markers, and PD-L1 expression were evaluated. Our findings demonstrate that in contrast to UPCI:SCC154 (HPV+ OSCC) cells, the SCC-9 (HPV− OSCC) cell line induced a highly activated functional state in neutrophils, which is potentially associated with a pro-tumorigenic effect. The HaCaT 16-E7 supernatant only stimulated the activation of some neutrophil functions. Understanding the complex interplay between neutrophils and their microenvironment has the potential to identify TANs as viable therapeutic targets. Full article
(This article belongs to the Special Issue The Tumor Microenvironment and Immunotherapy of Head and Neck Cancer)
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17 pages, 1825 KiB  
Article
Association of Tumor Microenvironment with Biological and Chronological Age in Head and Neck Cancer
by Martine Froukje van der Kamp, Eric Hiddingh, Julius de Vries, Boukje Annemarie Cornelia van Dijk, Ed Schuuring, Lorian Slagter-Menkema, Bert van der Vegt and Gyorgy Bela Halmos
Cancers 2023, 15(15), 3834; https://doi.org/10.3390/cancers15153834 - 28 Jul 2023
Cited by 1 | Viewed by 1157
Abstract
There is often a mismatch between the chronological and biological age of head and neck squamous cell carcinoma (HNSCC) patients. Treatment is based on chronological age, while biological age seems to be a better prognosticator for treatment toleration. This study investigated whether tumor [...] Read more.
There is often a mismatch between the chronological and biological age of head and neck squamous cell carcinoma (HNSCC) patients. Treatment is based on chronological age, while biological age seems to be a better prognosticator for treatment toleration. This study investigated whether tumor characteristics are associated with chronological and biological age. The relation with survival was also assessed. Prospectively collected data from 164 newly diagnosed HNSCC patients enrolled in the OncoLifeS database were analyzed. Biological age was assessed by a multidomain geriatric assessment. Several immunological markers were tested by immunohistochemistry on tissue microarray sections from the tumor. Disease-free survival (DFS), adjusted for chronological- and biological age, was assessed by univariable and bivariable analyses. In biologically old patients, a lower infiltration of CD163+ macrophages (p = 0.036) as well as CD4+ (p = 0.019) and CD8+ (p = 0.026) lymphocytes was found in the tumor microenvironment. Chronological older patients showed significantly lower PD-L1 combined positive scores (p = 0.030). Advanced tumor stage and perineural growth were related to a worse DFS. None of the immunological markers showed a significant association with DFS. Biological age might have a stronger influence on tumor microenvironment than chronological age. These findings should initiate clinical studies investigating the response to specific treatment regimens (e.g., immunotherapy) according to the biological age. Full article
(This article belongs to the Special Issue The Tumor Microenvironment and Immunotherapy of Head and Neck Cancer)
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Review

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28 pages, 1602 KiB  
Review
The Three-Dimensional In Vitro Cell Culture Models in the Study of Oral Cancer Immune Microenvironment
by Elaheh Dalir Abdolahinia and Xiaozhe Han
Cancers 2023, 15(17), 4266; https://doi.org/10.3390/cancers15174266 - 25 Aug 2023
Cited by 5 | Viewed by 2158
Abstract
The onset and progression of oral cancer are accompanied by a dynamic interaction with the host immune system, and the immune cells within the tumor microenvironment play a pivotal role in the development of the tumor. By exploring the cellular immunity of oral [...] Read more.
The onset and progression of oral cancer are accompanied by a dynamic interaction with the host immune system, and the immune cells within the tumor microenvironment play a pivotal role in the development of the tumor. By exploring the cellular immunity of oral cancer, we can gain insight into the contribution of both tumor cells and immune cells to tumorigenesis. This understanding is crucial for developing effective immunotherapeutic strategies to combat oral cancer. Studies of cancer immunology present unique challenges in terms of modeling due to the extraordinary complexity of the immune system. With its multitude of cellular components, each with distinct subtypes and various activation states, the immune system interacts with cancer cells and other components of the tumor, ultimately shaping the course of the disease. Conventional two-dimensional (2D) culture methods fall short of capturing these intricate cellular interactions. Mouse models enable us to learn about tumor biology in complicated and dynamic physiological systems but have limitations as the murine immune system differs significantly from that of humans. In light of these challenges, three-dimensional (3D) culture systems offer an alternative approach to studying cancer immunology and filling the existing gaps in available models. These 3D culture models provide a means to investigate complex cellular interactions that are difficult to replicate in 2D cultures. The direct study of the interaction between immune cells and cancer cells of human origin offers a more relevant and representative platform compared to mouse models, enabling advancements in our understanding of cancer immunology. This review explores commonly used 3D culture models and highlights their significant contributions to expanding our knowledge of cancer immunology. By harnessing the power of 3D culture systems, we can unlock new insights that pave the way for improved strategies in the battle against oral cancer. Full article
(This article belongs to the Special Issue The Tumor Microenvironment and Immunotherapy of Head and Neck Cancer)
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