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      Tumor microenvironment and immune-related therapies of head and neck squamous cell carcinoma

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          Abstract

          Head and neck squamous cell carcinomas (HNSCCs) are a type of common malignant tumor, mainly manifesting as oropharyngeal, oral cavity, laryngopharyngeal, hypopharyngeal, and laryngeal cancers. These highly aggressive malignant tumors reportedly affect more than 830,000 patients worldwide every year. Currently, the main treatments for HNSCC include surgery, radiotherapy, chemotherapy, and immunotherapy, as well as combination therapy. However, the overall 5-year survival rate of HNSCC has remained 50%, and it has not significantly improved in the past 10 years. Previous studies have shown that the tumor microenvironment (TME) plays a crucial role in the recurrence, metastasis, and drug resistance of patients with HNSCC. In this review, we summarize the role of anti-tumor and pro-tumor immune cells, as well as extracellular components in the TME of HNSCC. We also discuss classical HNSCC immunotherapy and highlight examples of clinical trials using CTLA-4 inhibitors and programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1)-related combination therapies. We also outline some molecules in the TME known to regulate immunosuppressive cells. Furthermore, the role and underlying mechanism of radiation therapy on the TME, immune cells, and immune response are discussed.

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          Abstract

          The tumor microenvironment (TME) plays a critical role in the recurrence, metastasis, and resistance of cancers. Wu and colleagues present an overview of the TME and immunotherapy in head and neck squamous cell carcinoma (HNSCC), together with a discussion of the effects and prospects of radiotherapy on the TME and HNSCC treatment.

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          Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

          Ahmedin Jemal, Lindsey A Torre, Rebecca Siegel … (2018)
          This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths), closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality). Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality. The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors. It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries. The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts. CA: A Cancer Journal for Clinicians 2018;0:1-31. © 2018 American Cancer Society.
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            Global cancer statistics, 2012.

            Lindsey A Torre, Freddie Bray, Rebecca Siegel … (2015)
            Cancer constitutes an enormous burden on society in more and less economically developed countries alike. The occurrence of cancer is increasing because of the growth and aging of the population, as well as an increasing prevalence of established risk factors such as smoking, overweight, physical inactivity, and changing reproductive patterns associated with urbanization and economic development. Based on GLOBOCAN estimates, about 14.1 million new cancer cases and 8.2 million deaths occurred in 2012 worldwide. Over the years, the burden has shifted to less developed countries, which currently account for about 57% of cases and 65% of cancer deaths worldwide. Lung cancer is the leading cause of cancer death among males in both more and less developed countries, and has surpassed breast cancer as the leading cause of cancer death among females in more developed countries; breast cancer remains the leading cause of cancer death among females in less developed countries. Other leading causes of cancer death in more developed countries include colorectal cancer among males and females and prostate cancer among males. In less developed countries, liver and stomach cancer among males and cervical cancer among females are also leading causes of cancer death. Although incidence rates for all cancers combined are nearly twice as high in more developed than in less developed countries in both males and females, mortality rates are only 8% to 15% higher in more developed countries. This disparity reflects regional differences in the mix of cancers, which is affected by risk factors and detection practices, and/or the availability of treatment. Risk factors associated with the leading causes of cancer death include tobacco use (lung, colorectal, stomach, and liver cancer), overweight/obesity and physical inactivity (breast and colorectal cancer), and infection (liver, stomach, and cervical cancer). A substantial portion of cancer cases and deaths could be prevented by broadly applying effective prevention measures, such as tobacco control, vaccination, and the use of early detection tests. © 2015 American Cancer Society.
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              The Tumor Microenvironment Innately Modulates Cancer Progression

              Dominique C. Hinshaw, Lalita A Shevde (2019)
              Cancer development and progression occurs in concert with alterations in the surrounding stroma. Cancer cells can functionally sculpt their microenvironment through the secretion of various cytokines, chemokines, and other factors. This results in a reprogramming of the surrounding cells, enabling them to play a determinative role in tumor survival and progression. Immune cells are important constituents of the tumor stroma and critically take part in this process. Growing evidence suggests that the innate immune cells (macrophages, neutrophils, dendritic cells, innate lymphoid cells, myeloid-derived suppressor cells, and NK cells) as well as adaptive immune cells (T cells and B cells) contribute to tumor progression when present in the tumor microenvironment (TME). Crosstalk between cancer cells and the proximal immune cells ultimately results in an environment that fosters tumor growth and metastasis. Understanding the nature of this dialog will allow for improved therapeutics that simultaneously target multiple components of the TME, increasing the likelihood of favorable patient outcomes.
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                Author and article information

                Contributors
                Wei Gao
                Binquan Wang
                Yongyan Wu
                Journal
                Journal ID (nlm-ta): Mol Ther Oncolytics
                Journal ID (iso-abbrev): Mol Ther Oncolytics
                Title: Molecular Therapy Oncolytics
                Publisher: American Society of Gene & Cell Therapy
                ISSN (Electronic): 2372-7705
                Publication date PMC-release: 21 January 2021
                Publication date Collection: 26 March 2021
                Publication date (Electronic): 21 January 2021
                Volume: 20
                Pages: 342-351
                Affiliations
                [1 ]Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi, China
                [2 ]Department of Otolaryngology Head & Neck Surgery, First Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi, China
                [3 ]Shanxi Province Clinical Medical Research Center for Precision Medicine of Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi, China
                [4 ]Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan 030001 Shanxi, China
                [5 ]Department of Cell Biology and Genetics, Basic Medical School of Shanxi Medical University, Taiyuan 030001, Shanxi, China
                [6 ]Department of Biochemistry & Molecular Biology, Shanxi Medical University, Taiyuan 030001, Shanxi, China
                Author notes
                [∗ ]Corresponding author: Yongyan Wu, PhD, Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi, China. wuyongyan@ 123456sxent.org
                [∗∗ ]Corresponding author: Binquan Wang, MD, Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi, China. wbq_xy@ 123456sxent.org
                [∗∗∗ ]Corresponding author: Wei Gao, MD, Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi, China. gaoweisxent@ 123456sxent.org
                Article
                Publisher Item ID: S2372-7705(21)00012-7
                DOI: 10.1016/j.omto.2021.01.011
                PMC ID: 7878981
                PubMed ID: 33614915
                SO-VID: 75b3c3e1-647a-4f7f-a887-a03c71891fb2
                Copyright © © 2021 The Author(s)
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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                Subject: Review

                Keywords: head and neck squamous cell carcinoma,tumor microenvironment,immunotherapy,pd-1,pd-l1,ctla-4
                Data availability:
                Keywords: head and neck squamous cell carcinoma, tumor microenvironment, immunotherapy, pd-1, pd-l1, ctla-4

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