Volume 4 Issue 7, July 2023

Mark A. Dawson obtained his medical degree from the University of Melbourne, followed by a PhD from the University in Cambridge. From 2010 to 2014, he was a Wellcome-Beit fellow at the University of Cambridge, and thereafter he joined the Peter MacCallum Cancer Centre as a consultant hematologist and group leader of the cancer epigenetics laboratory. In 2016, he was appointed co-program head of the Cancer Biology and Therapeutics Program, and in 2019 as associate director for research.

Therapeutic products containing CD8⁺ and CD4⁺ T cells expressing CARs are effective at inducing remission in patients with cancer. How CD4⁺ CAR T cells contribute to the anti-tumor response has not been well established. A study uses syngeneic models and in vivo imaging to glean mechanistic insights into how CD4⁺ T cells target tumors.

Pathological diagnosis relies on morphological assessment of tissue using histological staining and molecular phenotyping through immunostaining that must be performed on separate tissue sections. Orion is a newly reported methodology that facilitates multiplexed immunostaining with histological staining on the same slide.

Tyrosine kinase inhibitors that target anaplastic lymphoma kinase (ALK) have greatly improved the survival of patients with ALK-rearranged non-small-cell lung cancer, but they are insufficient to achieve a complete cure. A newly developed vaccine elicited a strong immune response specifically against ALK that eradicated primary tumors and prevented the onset of metastatic disease in mice.

Chimeric antigen receptor (CAR) T cells are effective for the treatment of therapy-resistant blood cancers but not solid tumors. We used a well-studied mutant c-KIT protein (c-KIT D816V) as a co-stimulatory domain to generate CAR T cells with strong IFNγ signaling that were able to overcome the immunosuppressive microenvironment of solid tumors.

Samuels and colleagues review the landscape of cancer peptide antigens, focusing on emerging concepts and the latest translational and clinical advances.

Brastianos and colleagues discuss the molecular and microenvironmental features of brain metastases, as well as promising avenues in translational research to overcome challenges for effective treatments.

Bousso and colleagues show that IFN-γ production is the dominant tumor elimination mechanism exerted by CD4⁺ CAR T cells and define tumor cell sensitivity to IFN-γ as a determinant of CD4⁺ CAR T efficacy.

Using genetically engineered models, Genovese and colleagues study patterns of convergent evolution in renal cancer, and pinpoint dysregulation of interferon signaling as a means of adaptation to chromosomal instability in metastatic progression.

Xiong et al. engineer CAR T cells to express the c-Kit D816V mutation, which enhances antigen-dependent proliferation and cytotoxicity, translates into extended survival in solid tumor models and is controllable by tyrosine kinase inhibitors.

Mota et al. show that poor response to immune checkpoint blockade in mouse models of ALK-rearranged NSCLC can be overcome by vaccination with an immunogenic ALK peptide and identify immunogenic human ALK peptides for future translational study.

Sorger and colleagues present Orion, a technique to analyze H&E histology and multiplex immunofluorescence imaging data from the same cells, which they apply to human colorectal cancer samples to identify spatial biomarkers of disease progression.