TCF1⁺ progenitor-exhausted CD8⁺ T cell populations mediate durable antitumor immunity. Upon antigenic stimulation, effector T cells upregulate aerobic glycolysis to support their cytotoxic phenotype. Here, Mittal and colleagues find that loss of metabolic regulator PKM2 enriches for TCF1⁺ progenitor-exhausted-like cells and improves responsiveness to PD-1 blockade.

Saeki and colleagues show that IRF8 defines the epigenetic landscape in postnatal microglia, thereby directing their transcriptome programs.

Zhou and colleagues find that GPR34 is a metabolic immune checkpoint for ILC1-mediated antitumor immunity.

Herbert and colleagues show MrgprA3⁺ neurons activate myeloid cells to promote cutaneous IL-17-dependent immunity against Schistosoma mansoni.

Zhou and colleagues find that GPR34 is a metabolic immune checkpoint for ILC1-mediated antitumor immunity.

Herbert and colleagues show MrgprA3⁺ neurons activate myeloid cells to promote cutaneous IL-17-dependent immunity against Schistosoma mansoni.

TCF1⁺ progenitor-exhausted CD8⁺ T cell populations mediate durable antitumor immunity. Upon antigenic stimulation, effector T cells upregulate aerobic glycolysis to support their cytotoxic phenotype. Here, Mittal and colleagues find that loss of metabolic regulator PKM2 enriches for TCF1⁺ progenitor-exhausted-like cells and improves responsiveness to PD-1 blockade.

Saeki and colleagues show that IRF8 defines the epigenetic landscape in postnatal microglia, thereby directing their transcriptome programs.

PD-1 is a critical modulator of CD8⁺ T cell activation and exhaustion. Sen and colleagues show that a cell-state-specific enhancer tunes PD-1 expression exclusively in exhaustion and that deletion of this enhancer improves CD8⁺ T cell function.

When monkeys are infected with a virus similar to HIV, treated with antiretroviral therapy (ART), and are administered a ‘combo therapy’ made of antibodies against molecules that inhibit immune responses, they control viral rebound when ART is discontinued for more than 6 months

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.