Volume 1 Issue 11, November 2020

Recent advances in cancer neuroscience necessitate the systematic analysis of neural influences in cancer as potential therapeutic targets in oncology. Here we outline recommendations for future preclinical and translational research in this field.

Invariant natural killer T cells (iNKT cells) are innate-like CD1d-restricted T cells that have NK cell–like properties and bear an invariant T cell receptor (iTCR). iNKT cells have shown potential for cancer immunotherapy. A study now shows that stabilization of the iTCR–CD1d complex via a single-chain bi-specific antibody stimulates iNKT cell–mediated anti-tumor immunity.

Tumor-specific changes in DNA methylation are both acquired actively through transcription-coupled processes and passively accumulated over time. Analysis across B cell malignancies now shows that these changes provide insight into the cellular origin as well as the proliferative history of tumors and thereby have diagnostic value and prognostic value, respectively.

Although RET alterations are relatively frequent across tumor types, specific targeting of RET in the clinic has been challenging. Ambrogio, Aggarwal and colleagues provide their views on how mechanistic studies have swiftly translated into powerful targeted therapies in two recent clinical studies that led to the FDA approval of selpercatinib for certain tumors in which RET is altered.

Beltran and colleagues discuss the challenges in treating metastatic prostate cancer and strategies to accelerate precision oncology and improve therapy and clinical decisions in this setting.

Rossjohn, van der Vliet and colleagues develop single-domain antibodies binding composite CD1d and NKT T-cell receptor antigens, inducing specific antitumor immune subsets.

Martin-Subero and colleagues analyze DNA methylation patterns in B-cell tumors and their normal cells of origin, and develop epiCMIT, a methylation-based mitotic clock with prognostic relevance.

Using lineage tracing and molecular profiling, Abate-Shen and colleagues identify a Ras and Myc co-activation signature that predicts metastasis and castration resistance in localized prostate cancer.

Using single-cell RNA sequencing, CyTOF and multiplex immunohistochemistry, Steele et al. survey the immune landscape in pancreatic cancers, adjacent tissue and blood, observing heterogeneous immune checkpoint receptor expression within patients.

Ferrando and colleagues analyze matched diagnostic and relapsed acute lymphocytic leukemia by whole-genome sequencing, and perform in vitro genome-wide CRISPR screens, to examine alterations associated with chemotherapy resistance.