Highlights of This Issue

Resistance to PD-(L)1 immune checkpoint inhibitors (ICI) is common in non–small-cell lung cancer (NSCLC) patients. Trefny and colleagues have identified KIR3DS1, a genetic variation of a NK cell receptor, as a mediator of resistance to ICI in NSCLC patients. The KIR3DS1 variant and NK cell dysfunction were linked to clinical progression under PD-(L)1 therapy. This finding offers a new therapeutic approach to overcome such resistance by targeting NK cells, thus establishing effective antitumor immunity.

The etiopathogenesis of mature T-cell lymphomas is still an enigma. Mycosis fungoides (MF), the most common cutaneous T-cell lymphoma, is thought to be caused by malignant transformation of a mature T cell residing in the skin. To pinpoint the relationship between the neoplastic cells in biopsies from MF tumors, Hamrouni and colleagues performed a detailed analysis of the T-cell receptor rearrangements using deep sequencing. They found evidence strongly supporting the notion that malignant cells are clonally diverse and probably originating from an immature precursor cell. New therapeutic strategies should therefore target those early lymphoma precursor cells.

Aberrant trans-splicing-induced GOLM1-NAA35 chimeric RNA is enriched in human esophageal squamous cell carcinoma and correlates with patient outcome. Because saliva collection is noninvasive and painless, Lin and colleagues evaluated the clinical utility of salivary exosomal GOLM1-NAA35 as a candidate esophageal cancer biomarker using human cells, a mouse model, and saliva samples from several patient cohorts. The discoveries highlight a new approach with translational clinical potential as a convenient, nonradiological and noninvasive test for early cancer detection, therapeutic response measurement, and close monitoring for recurrence.

The high false-positive rate of prostate-specific antigen (PSA) may lead to unnecessary prostate biopsy, an invasive procedure that can cause severe complication. In this study, Urabe and colleagues analyzed microRNA microarray data from 1,091 serum samples of prostate cancer (PCa), negative prostate biopsy, and healthy controls to identify a potential screening diagnostic tool for PCa. They found the combination of two miRNAs was able to detect PCa in men with suspected PCa. This model could help reduce the number of unnecessary biopsies and improve the accuracy of diagnosis.