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.
Human cytomegalovirus (HCMV) infection can have long-term immune effects, and NK and T cells both play roles in keeping HCMV latent. Based on the knowledge that CD8+ T cells can display NK cell-like properties, and that these cells can have a beneficial presence in individuals infected with particular intracellular pathogens causing tuberculosis or leprosy, Sottile et al. investigated this subset and determined the phenotype, transcriptomics, and reactivity of NKG2C+CD8+ T cells after HCMV ex...
Treatment of tumors with cytokines to boost antitumor immune responses is limited in the clinic due to systemic adverse events. Intratumoral delivery of cytokines may overcome these issues and improve therapeutic efficacy. Hotz and Wagenaar et al. thoroughly investigated the efficacy of local delivery of mRNA encoding a mixture of cytokines alone or combined with checkpoint blockade in murine models to take advantage of these powerful immune stimulants.
Dream team: TGFβ and PD-L1 targeting aligns with radiotherapy to create a beneficial immune environment
Since radiotherapy (RT) can boost immune priming, it can be a great tool to convert immune “cold” tumors into “hot” immune environments, making way for effective checkpoint inhibition therapies. However, RT may also remodel the tumor microenvironment (TME), creating barriers to immune infiltration and antitumor effects. Given that one of the main contributors to TME remodeling is the TGFβ pathway, combining RT with neutralization of TGFβ and checkpoint blockade may effectively treat cold tumo...
Treatment of solid tumors with CAR T has various barriers to overcome to be effective. To improve efficacy, boosting the immune response by delivering pattern recognition receptor (PRR) agonists more specifically to immune than tumor cells might improve responses, given the known role of some PRRs to drive tumor progression. To do this, Johnson et al. engineered a CAR that delivers the RNA RN7SL1 preferentially to immune cells, and tested its use and effects on endogenous immune responses in ...
Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis and is largely refractory to current clinical immunotherapies. Freed-Pastor et al. investigated the immune evasion mechanisms in this cancer type by assessing neoantigen load, neoantigen-specific T cells, and T cell characteristics, revealing a novel axis of inhibition. Their results were recently published in Cancer Cell.
Even though MAPK inhibitors (MAPKi, such as BRAFi or MEKi) can be an effective treatment strategy, therapy resistance limits their benefits. However, in clinical studies, patients with BRAFV600E/K metastatic melanoma, who had received prior treatment with checkpoint inhibitors, had increased efficacy of MAPKi with longer progression-free survival.
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.