Head and neck squamous cell carcinoma (HNSCC) is a very aggressive disease with a poor prognosis for advanced-stage tumors. Recent clinical, genomic, and cellular studies have revealed the highly heterogeneous and immunosuppressive nature of HNSCC. Despite significant advances in multimodal therapeutic interventions, failure to cure and recurrence are common and account for most deaths. It is becoming increasingly apparent that tumor microenvironment (TME) plays a critical role in HNSCC tumorigenesis, promotes the evolution of aggressive tumors and resistance to therapy, and thereby adversely affects the prognosis. A complete understanding of the TME factors, together with the highly complex tumor–stromal interactions, can lead to new therapeutic interventions in HNSCC. Interestingly, different molecular and immune landscapes between HPV+ve and HPV−ve (human papillomavirus) HNSCC tumors offer new opportunities for developing individualized, targeted chemoimmunotherapy (CIT) regimen. This review highlights the current understanding of the complexity between HPV+ve and HPV−ve HNSCC TME and various tumor–stromal cross-talk modulating processes, including epithelial–mesenchymal transition (EMT), anoikis resistance, angiogenesis, immune surveillance, metastatic niche, therapeutic resistance, and development of an aggressive tumor phenotype. Furthermore, we summarize the recent developments and the rationale behind CIT strategies and their clinical applications in HPV+ve and HPV−ve HNSCC.
Head and neck squamous cell carcinomas (HNSCCs) are aggressive diseases with a dismal patient prognosis. Despite significant advances in treatment modalities, the five-year survival rate in patients with HNSCC has improved marginally and therefore warrants a comprehensive understanding of the HNSCC biology. Alterations in the cellular and non-cellular components of the HNSCC tumor micro-environment (TME) play a critical role in regulating many hallmarks of cancer development including evasion of apoptosis, activation of invasion, metastasis, angiogenesis, response to therapy, immune escape mechanisms, deregulation of energetics, and therefore the development of an overall aggressive HNSCC phenotype. Cytokines and chemokines are small secretory proteins produced by neoplastic or stromal cells, controlling complex and dynamic cell–cell interactions in the TME to regulate many cancer hallmarks. This review summarizes the current understanding of the complex cytokine/chemokine networks in the HNSCC TME, their role in activating diverse signaling pathways and promoting tumor progression, metastasis, and therapeutic resistance development.
A Correction to this paper has been published: https://doi.org/10.1038/s41392-021-00503-9
Trichuris (whipworms) is a type of roundworm that is responsible for trichuriasis in human beings. Globally, 600–800 million people are infected by this helminthic worm per year. Trichuris is more prevalent in some tropical and sub-tropical areas such as East Asia, China, Sub-Saharan Africa, and the Americas. These parasitic nematodes affect the small intestines of mammals, causing a great deal of discomfort. Their life cycle is completed in two stages; mammals and the external environment. The zoonotic transmission of the disease is responsible for huge infections and deaths around the world. In recent times, researchers have gained a lot of understanding about the genetics and parasitology of Trichuris. In this chapter, we will discuss the origin, phylogeny, life cycle, diagnosis, and zoonotic transmission of the parasite. At the same time, the chapter discusses the genomics of the parasite and the future directions that can help us contain this parasitic nematode.
The Himalayas are home to a wide variety of animals and plants, making it one of the world's most biodiverse regions. Both the northwestern Himalayan region of Jammu & Kashmir and the trans-Himalayan region of Ladakh are home to a wide variety of bird species because of varied topography and temperature. In this study, we collected the field data and checklists over a period of 3 years based on the compilation of data from published & unpublished scientific literature, print & electronic, currently accessible in the form of research articles, papers, books, websites, web pages, & field notes. The Northwestern Himalayas (Jammu and Kashmir) and trans-Himalayas (Ladakh) are home to 677 bird species belonging to 89 families (out of 107 families in the Indian sub-continent), which is equal to 6.77% of total bird species (>10000) found globally and 49.2% of total bird species (1376) found in the Indian subcontinent. The family Muscicapidae (53, 7.8%) has the most species, followed by Accipitridae (41, 6%), and so on. Moreover, the number of threatened species is 54 (8%), which includes 22 (3.25%), 23 (3.40%), 6 (0.8%) & 3 (0.44%) under Near Threatened, Vulnerable, Endangered, & Critically Endangered categories. Among 677 species, 228 species (33.77%) are found in all the 3 regions, 77 (11.4%) in only Jammu & Kashmir but not Ladakh, 24 (3.55%) in Jammu & Ladakh but not in Kashmir, 80 (11.85%) in Kashmir & Ladakh but not in Jammu, 152 (22.5%) only in Jammu but not in Kashmir & Ladakh, 26 (3.84%) only in Kashmir but not in Jammu & Ladakh, 71 (10.51%) only in Ladakh but not in Jammu & Kashmir. This provides the first-of-its-kind comprehensive data on bird diversity in these regions.
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