Maartje Wouters is a freelance science and medical writer. She has obtained a PhD in cancer immunology from the University of Groningen and is specialized in oncology, immunology, and healthy aging.
Regulatory T cells (Treg) can differentiate into follicular regulatory T cells (TFR) that have important roles in secondary lymphoid organs and may have higher suppressive activity. However, their role in antitumor immunity has not been elucidated. Eschweiler et al. investigated the role of TFR in cancer, analyzing their function, characteristics, and effects on the efficacy of checkpoint inhibition using RNAseq of human cancer cohorts and mouse models.
Since the first vaccines for COVID-19 were authorized for use in various countries in December 2020 and January 2021, a mass vaccination campaign has started all over the world. Six months later, when we look at the balance, we see that some countries are starting to really feel the benefits of it. But many countries lag behind.
What is the current status in the world?
Tumors with a low mutational burden generally respond poorly to immunotherapy. Given that radiotherapy can induce mutations in tumor cells and has been found to synergize with immunotherapy, Lussier, Alspach, and Ward et al. explored whether radiation of low mutation burden tumor cells induces neoantigens that can be recognized by T cells to improve checkpoint therapy responses.
While immunotherapies work great in some patients, for most, results are limited. One reason for the limited therapeutic response is the induction of an “exhausted” phenotype in CD8+ TILs. Aiming to reinvigorate exhausted CD8+ TILs in the TME, Guo and Xie et al. explored the effects of IL-10 treatment and combined it with adoptive cell transfer (ACT) and checkpoint blockade in various animal models; their data were recently published in Nature Immunology.
Clinically, heterogeneous immune responses have been detected between patients, between tumors in the same patient, and even by disease site. Some tumor microenvironments (TME) are typically immune cold and respond poorly to immunotherapy, such as pancreatic ductal carcinoma (PDAC). However, there are some exceptions, which provides the hope that a mechanistic understanding of any differences will provide better therapeutic opportunities.
A group of vaccines that work in a similar way, based on a viral vector for the delivery of the vaccine information, are those developed by AstraZeneca and the University of Oxford (also named Covishield and Vaxzevria), Johnson and Johnson (J&J, Janssen), the in Russia developed vaccine called Sputnik V (Gamaleya), and the in China developed CanSinoVaccine.
Given that only a subset of patients responds to current checkpoint inhibition therapies, the search for new immune checkpoint targets continues. Sharma et al. identified and investigated one such new target, LILRB4, in mouse and human tumors, and assessed the effects of blockade in a variety of mouse models. Their results were recently published in the Journal of Experimental Medicine.
The start of the pandemic activated many researchers and pharmaceutical companies to start developing vaccines against the virus SARS-CoV-2. Multiple different techniques are used for these vaccines. Some have obtained approval to be used in people, while others are still in various stages of development.
Below we provide an overview of the main types of vaccines available or in development.
Cancer stem cells (CSCs) are considered the “seeds” of tumor metastasis, but how these cells escape the effects of chemotherapy and immune surveillance is unclear. Wang et al. previously detected CSCs with a limited expression of PD-L1 in head and neck squamous cell carcinoma (HNSCC). In an attempt to detect other targetable checkpoints expressed by these cells, the researchers investigated expression and modulation of another B7 family member, CD276 (B7-H3), in a mouse model for HNSCC.
Exitrons are internal regions of an exon that have both protein-coding and splicing potential. When these exitrons are spliced, it may lead to protein isoforms, including in-frame deletions, as well as out-of-frame neo open reading frames. As not much is known about the abundance or impact of exitrons in cancer, Wang and Liu et al. quantitatively assessed exitrons in cancer using bioinformatics analyses, revealing functional roles, as well as a new potential source of neoantigens.
The first two COVID-19 vaccines that finished clinical trials and were cleared for use in multiple countries were the Pfizer-BioNTech and Moderna vaccines. Both these vaccines use mRNA.
What is mRNA?
The m in mRNA stands for messenger, and RNA is an abbreviation for ribonucleic acid. The mRNA is a code for the cell to produce a protein. This is similar to an instruction manual on how to create a protein. A small cell component, the ribosome, produces the protein based on the mRNA.
Our bodies have a very sophisticated system within them to protect us from encounters by intruders that may harm us, such as viruses and bacteria. The immune system consists of specifically trained cells and also includes physical barriers such as the skin and mucous membranes that limit intruders to make it into the body. The immune cells are mainly found in the blood but patrol the whole body.
Lymphangiogenesis, the growth of lymphatic vessels, has contradictory consequences in cancer; within the tumor, it is associated with metastasis and poor prognosis, but outside of the tumor, it can boost T cell immunity. Using this knowledge, Sasso et al. developed a cancer vaccine strategy to increase tumor control and immune memory. The preclinical data on this approach were recently published in Science Advances.
Virus-specific tumor-infiltrating T cells have previously been considered bystander cells not contributing to the antitumor response in the same way that T cells specific to tumor-associated antigens (TAAs) might. To begin to unpack the vast amount of TCR sequence data available from tumor and normal tissue samples, Chiou and Tseng et al. used the algorithm GLIPH2 to identify groups of TCRs with similar antigen specificities in a large cohort of patients with non-small cell lung cancer...
The helper function of CD4+ T cells in antitumor immune responses has been characterized, but much less is known about the role of cytotoxic CD4+ Th cells (Th-CTX) in tumors. Cachot, Bilous, and Liu et al. investigated the presence, phenotype, and cytolytic function of tumor-specific Th-CTX using single-cell transcriptomics, peptide–MHC-II multimers, and a newly developed high-throughput single-cell cytotoxicity assay. Their exciting results were recently published in Science Advances.