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Effector CD8⁺ T cells with cytotoxic ability are crucial for immunotherapy success. Two studies show that salt (NaCl) supplementation can enhance the effector function of CD8⁺ T cells and boost their antitumor responses.

Immunocytokines are cytokine-based fusion proteins with therapeutic potential. New CD45-targeted immunocytokines can reprogram systemic anti-tumor immunity by prolonged retention on T cells and dendritic cells while minimizing systemic toxicities through intratumoral delivery.

This Comment discusses the explosion in innovative systems biology approaches in infectious disease studies. We outline the numerous challenges associated with these technologies from standardizing data science approaches to reproducibility of findings, as well as cost.

Tumor cells in emerging cancers modify their gene expression to avoid immune control, a process known as immunoediting. We found that genome-wide gene expression changes in breast tumors after oncogene induction in genetically engineered mice were dominated by the epigenetic repression of innate and adaptive immune genes. Immunoevasion by tumors was reversed by a DNA methyltransferase inhibitor.

Mucosal vaccine boosters are expected to enhance protection against SARS-CoV-2 infection. A study now reveals that the delivery device — through either intranasal sprayers or nebulizers — also influences the mucosal immunity and protection efficacy in non-human primates.

Seder and colleagues show that mucosal adenoviral-vectored vaccine boosting durably prevents infection in nonhuman primates of the highly transmissible, heterologous XBB.1.16 strain of SARS-CoV-2.

Here the authors pull apart the cellular composition of the tumor microenvironment using RNA sequencing data from a wide variety of cancer types. They identify immunity quantitative trait loci and integrate these data with analysis of colorectal cancer cohorts, creating a polygenic risk score and a database for community access.

A distinct subset of attenuated CD8⁺ T cells that retain crucial cytotoxic functions has been identified in chronic hepatitis B infection and linked to viral control.

In this paper and the related paper from Lugli and colleagues the authors show that high levels of NaCl inside the tumor have a beneficial effect on CD8⁺ T cells and their ability to control tumor growth as a result of enhanced T cell receptor activity.

Heim et al. investigate the role of CD8⁺ T cells specific to HBV polymerase in the context of chronic HBV infection. They identify a unique subset of CD8⁺ T cells with an attenuated effector function. The attenuation is driven by TGFβ signaling, offering new insights into the immune landscape of chronic HBV infection and suggesting potential therapeutic avenues for modulating these cells to enhance viral control.

Along with a back-to-back published paper from Zielisnki and co. in this issue of Nature Immunology, this paper shows that NaCl affects CD8⁺ T cell function by counteracting the exhaustion of these cells in the tumor microenvironment.

Seder and colleagues review the latest scientific advances in understanding how monoclonal antibodies to the circumsporozoite protein prevent malaria and highlight how this emerging intervention can be used alone or alongside existing antimalarial interventions to control malaria across at-risk populations.

Here the authors present a mass cytometry-based method for identification of antigen-specific T cells and their differentiation state, testing it in cancer, bacterial and viral mouse models.

HIV-specific CD8⁺ T cells are dysfunctional in the majority of people living with HIV. However, long-term treatment with antiretroviral therapy may considerably improve the antiviral function of these cells.

Here the authors provide a resource for ovarian cancer combining spatial transcriptomics, genomics, CRISPR Perturb-seq screens and in silico methods to focus on T cells and natural killer cells in the tumor and their role in immune evasion.

Appay and colleagues show that long-term antiretroviral therapy is associated with clonal succession of HIV-1-specific CD8⁺ T cell populations, which evolved from an exhaustion-like toward a stemness-like phenotype.