Volume 2 Issue 9, September 2021

Combining radiation and immune checkpoint blockade is a promising treatment strategy, yet the mechanisms and optimal dosing strategies are not well known. A new study finds that a specific radiation dose can activate secretory club cells to promote the anti-tumor effects of radiotherapy combined with immunotherapy in NSCLC.

CAR T cell therapies have made great strides in the clinic; however, multiple hurdles limit the efficacy of this approach for solid tumors. A new study has developed an optimized, dual-targeting CAR T cell that overcomes several of these challenges by enhancing T cell persistence and reducing therapy escape due to antigen loss.

Pseudouridine is the most abundant RNA modification, but its biological role remains poorly understood. A study now finds dysregulated pseudouridine synthase PUS7 in glioblastoma and demonstrates that pharmacological inhibition of PUS7 leads to reduced tumorigenesis, which underpins the therapeutic potential of targeting epitranscriptomic regulators in cancer.

Ding and colleagues discuss the era of pan-cancer analysis, covering the fundamental insights gained, unique opportunities and challenges, and the future of such approaches in the basic and clinical space.

Yarchoan and colleagues present a single-arm phase 1 clinical trial of cabozantinib with immune checkpoint inhibition for patients with hepatocellular carcinoma. Using high-dimensional spatial analysis, they identify immune features enriched in responders.

Dotti and colleagues present a CAR design featuring trans-acting CD28 and 4-1BB co-stimulation and shared CD3ζ-chain, which improved CAR-T cell metabolic and antitumor functions and avoided tumor escape through simultaneous targeting of two antigens.

Mittal and colleagues investigate the mechanisms underlying the therapeutic effects of radiation therapy in combination with checkpoint blockade, finding a role for activated lung-resident secretory club cells in modulating antitumor immune responses.

Shi and colleagues show that PUS7 controls tRNA pseudouridylation and codon-specific translation to fuel glioblastoma tumorigenesis, and discover a PUS7 inhibitor that delays tumor growth in glioblastoma models.

Manczinger and colleagues define ‘promiscuity’ as a feature of HLA-I alleles representing peptide repertoire breadth; promiscuous alleles may promote a more tolerant tumor microenvironment and negatively impact tumor immune surveillance.

Tanaka and colleagues perform a comprehensive multi-omic characterization of peritoneal metastasis of gastric cancer to define molecular subtypes and actionable therapeutic targets.

Chinnaiyan and colleagues perform a high-throughput compound screen and identify PIKfyve inhibition as a therapeutic strategy to enhance immune checkpoint blockade responses in advanced prostate cancer.