See article by Lo Russo et al., p. 989

Hyperprogression (HP) is a paradoxical boost in tumor growth described in a subset of patients treated with immune checkpoint inhibitors that has ignited an international debate on whether this phenomenon is true or only representative of a worse prognosis. Mimicking HP in preclinical models with distinctive genetic profile allowed Lo Russo and colleagues to uncover a critical role of innate immunity in this process that involves the interaction of anti-PD-1 antibody-Fc with FcR on M2-like macrophages. A distinctive immunophenotype of HP tumors characterized by clustered macrophages with epithelioid morphology is potentially able to predict HP.

See article by Richard et al., p. 957

Anti-PD-1 antibodies are approved for non-small cell lung cancer treatment, yet only one-quarter of patients benefit from this therapy. PD-L1 labelling and mutational tumor burden could help the clinician to predict outcome; however, optimal predictive biomarkers are lacking. This study by Richard and colleagues demonstrates that exome analysis before initiation of nivolumab therapy can be highly predictive of PFS and OS when analyzed in multiple dimensions, rather than using only mutational tumor burden. These findings have far-reaching implications in this age of precision medicine for an efficient immunotherapy and should increase the interest of complex analysis of exome for precision medicine in immuno-oncology.

See article by Audenet et al., p. 967

Urothelial carcinomas of the upper tract (UTUC) and bladder (UCB) exhibit similar histologic appearance but have distinct clinical and molecular characteristics. To investigate genomic differences between UTUC and UCB, Audenet and colleagues leveraged a prospective molecular characterization initiative to analyze 649 urothelial carcinomas using a targeted next-generation sequencing (NGS) platform. They identified significant differences in the prevalence of common genomic alterations. However, in individual patients with a history of both tumors, the UCB and UTUC were always clonally related. Furthermore, targeted NGS was a robust methodology for identifying UTUC patients in need of germline analysis for Lynch syndrome.

See article by Lin et al., p. 1050

The bifunctional roles of SCAN-Zinc finger transcription factor MZF1 in carcinogenesis remains unclear. Based on their previous observations that the garlic-derived compound diallyl trisulfide (DATS) suppresses gastric cancer (GC) growth and enhances its chemosensitivity through epigenetic upregulation of MT2A to attenuate NF-κB activation, Lin and colleagues found an association of MZF1 with MT2A in human GC cell lines and primary tumors, and reveal that MT2A recruits MZF1 to form MT2A/MZF1 complex binding to NFKBIA promoter to establish an “MT2A/MZF1-NF-κB” pathway in suppressing gastric carcinogenesis and enhancing GC chemosensitivity. MT2A/MZF1 thus represents a diagnostic marker and a therapeutic target for GC.