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Meet the newest T cell checkpoint: CD38

Immune checkpoint blockade (ICB) can unleash immune responses against a variety of cancers, but its efficacy is often limited by T cell exhaustion. In addition to well established checkpoints like PD-1 and CTLA-4, T cell exhaustion has also been...

A bispecific antibody-drug conjugate targeting EGFR and HER3 in metastatic esophageal squamous cell carcinoma: a phase 1b trial

In a phase 1b trial, 82 patients with esophageal squamous cell carcinoma were treated with an anti-EGFR/HER3 bispecific antibody linked to a topoisomerase I inhibitor, at 2.0 or 2.5 mg/kg q3wks. Treat...

CD4+ T cells license Kupffer cells to reverse CD8+ T cell dysfunction induced by hepatocellular priming

Venzin and Beccaria et al. demonstrate that pre-activated CD4+ T cells actively license local hepatic APCs and restore antiviral CD8+ T cell function. HBV-specific CD4+ T cell receptor transgenic mice...

Multimodal delineation of a layer of effector function among exhausted CD8 T cells in tumors

Ray et al. discovered that Cd69 mRNA levels could be used to differentiate between potent and dysfunctional activation states among intratumoral CD69+CD8+ T cells. CD8 T cells with high Cd69 mRNA and ...

IGM-7354, an immunocytokine with IL-15 fused to an anti-PD-L1 IgM, induces NK and CD8+ T cell-mediated cytotoxicity of PD-L1 positive tumor cells

Desbois et al. generated IGM-7354, an IgM comprising ten PD-L1 binding sites which blocked PD-L1/PD-1 binding and a single IL15/IL15Rα complex which activated IL15Rβγ+ human NK and CD8+ T cells and re...

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Previous Digests

Vaccine with ICB sidekick unlock anti-melanoma T cell immunity

July 16, 2025

While personalized neoantigen vaccines have great potential, T cell responses induced by these vaccines often lack strength. Blass, Keskin, et al. aimed to improve T cell antitumor immunity by optimizing vaccine adjuvants and combining the vaccine with ICB. The...

Mutant p53 doesn’t just lose functions - it gains them

July 9, 2025

Mutations in the p53 gene are well known drivers of cancer due to the loss of tumor suppressor functions that are maintained by wild-type p53. However, in recent investigations, Mahat et al. found that a common mutant p53, p53R175H...

CD8s get by without a little help from their friends

July 2, 2025

During acute infections, the primary immune response depends on CD4+ T cells providing help to CD8+ T cells. However, many effector CD8+ T cells (Teff) can respond to pathogens independently of helper responses, but these cells respond poorly to...

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