Head and neck squamous cell carcinoma (HNSCC) encompass a group of complex entities of tumours affecting the aerodigestive upper tract. The main risk factors are strongly related to tobacco and alcohol consumption, but also HPV infection is often associated. Surgery, radiotherapy and/or chemotherapy are the standard treatments, though the 5-year overall survival is less than 50%. The advances in genomics, molecular medicine, immunology, and nanotechnology have shed a light on tumour biology which helps clinical researchers to obtain more efficacious and less toxic therapies. Head and neck tumours possess different immune escape mechanisms including diminishing the immune response through modulating immune checkpoints, in addition to the recruitment and differentiation of suppressive immune cells. The insights into the HNSCC biology and its strong interaction with the tumour microenvironment highlights the role of immunomodulating agents. Recently, the knowledge of the immunological features of these tumours has paved the way for the discovery of effective biomarkers that allow a better selection of patients with odds of improving overall survival through immunotherapy. Specially biomarkers regarding immune checkpoint inhibitors antibodies, such as anti-PD-1/PD-L1 and anti-CTLA-4 in combination with standard therapy or as monotherapy. New immunotherapies to treat head and neck cancer carcinomas, such as CAR T cells and nanoparticles have been the center of attention and in this review, we discuss the necessity of finding targets for the T cell in the cancer cells to generate CAR T cells, but also the relevance of evaluating specificity and safety of those therapies.

T cells play an important role to build up an effective immune response and are essential in the eradication of pathogens. To establish a long-lasting protection even after a re-challenge with the same pathogen, some T cells differentiate into memory T cells. Recently, a certain subpopulation of memory T cells at different tissue-sites of infection was detected—tissue-resident memory T cells (T_RM cells). These cells can patrol in the tissue in order to encounter their cognate antigen to establish an effective protection against secondary infection. The liver as an immunogenic organ is exposed to a variety of pathogens entering the liver through the systemic blood circulation or via the portal vein from the gut. It could be shown that intrahepatic T_RM cells can reside within the liver tissue for several years. Interestingly, hepatic T_RM cell differentiation requires a distinct cytokine milieu. In addition, T_RM cells express specific surface markers and transcription factors, which allow their identification delimited from their circulating counterparts. It could be demonstrated that liver T_RM cells play a particular role in many liver diseases such as hepatitis B and C infection, non-alcoholic fatty liver disease and even play a role in the development of hepatocellular carcinoma and in building long-lasting immune responses after vaccination. A better understanding of intrahepatic T_RM cells is critical to understand the pathophysiology of many liver diseases and to identify new potential drug targets for the development of novel treatment strategies.

Summary: Chronic hepatitis B is characterized by a decades-long evolving engagement between host immunity and the hepatitis B virus (HBV). Understanding the molecular characteristics of HBV-specific CD8 T cells linked to control of viral replication and antigenemia is essential to design effective immunotherapeutic modalities. Here we show that HBV-specific CD8 T cells, even during infection stages with extremely high viral loads, lack the features of terminally exhausted CD8 T cells observed in chronic HCV and HIV infection or cancer. Instead, we observe emerging gene expression programs over disease stages that correlate with increasing HBV control, which include a bona fide cytotoxic and T-cell localization program associated with low levels of viral replication, and a second NK-like T-cell program that combines expression of classical NK markers ( KIR s, KLR s, FCGR3A , TYROBP , IKZF2 ) with cytotoxic genes ( GZMB , GNLY , PRF1 ), which emerges with complete control of HBV viremia and antigenemia. We also found enrichment of both CD8 T-cell programs in HIV-specific CD8 T cells from HIV elite controllers, supporting a conserved role in controlling persistent viral infections with viral reservoirs.