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CAR T cells take TROP2 targeting to the next level

TROP2 is a fetal oncogene that is expressed in a number of cancer types, and while it can be successfully targeted by antibody–drug conjugates (ADCs), cancer cells often develop ADC resistance, either through loss of expression of the targeted TROP2...

PD-1-targeted cis-delivery of an IL-2 variant induces a multifaceted antitumoral T cell response in human lung cancer

Fusi and Serger et al. showed that PD-1–IL2v, comprising a PD-1 blocking antibody and an IL-2Rα-non-binding IL-2 variant, induced antitumor T cell activity in human PBMCs and CD8+ and CD4+Foxp3- TILs ...

Intra-tumoral hypoxia promotes CD8+ T cell dysfunction via chronic activation of integrated stress response transcription factor ATF4

Pauneto et al. demonstrated in patient samples and tumor models that hypoxic stress in the TME induced an integrated stress response (ISR) in tumor antigen-specific T cells through multiple ISR kinase...

ATOR-4066, a bispecific antibody targeting CD40 and CEACAM5, induces strong myeloid and T cell-dependent tumor immunity and synergizes with PD-1 blockade

Andersson et al. described preclinical studies of ATOR-4066, a bispecific antibody that targets CEACAM5, which is expressed on most gastrointestinal carcinomas and others, and agonizes CD40. In vitro,...

Interferon-induced senescent CD8+ T cells reduce anti-PD1 immunotherapy efficacy in early triple-negative breast cancer

Analyzing samples from patients with TNBC before and after treatment with neoadjuvant anti-PD-1, Fu, Jin, He, Chen, and Yang et al. found that enrichment for IFN-induced senescent CD8+ T cells predict...

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Previous Digests

All about CICON25!

September 24, 2025

The ACIR team attended the CRI-ENCI Ninth International Cancer Immunotherapy Conference (CICON) 2025 in Utrecht, The Netherlands. This week’s extensive special feature covers select talks from the conference. We have organized the content by topics below. Keynote addressMichel Sadelain...

Stressed out telomeres drive T cell malfunction

September 17, 2025

Tumor-infiltrating T cells are known to lose functionality in the tumor microenvironment and become dysfunctional or terminally exhausted, limiting antitumor immunity and immunotherapy responses. The drivers behind this process remain largely to be determined. Rivadeneira et al. investigated the...

Tired out T cells: aberrant glycosylation drives T cell exhaustion in early tumors

September 3, 2025

Changes in glycosylation are a hallmark of cancer, and recent work has suggested that branched N-glycans on T cells may play a role in limiting their antitumor activity. In recent work, Azevedo et al. investigated the T cell glycome...

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