Highlights of This Issue

Neuroendocrine tumors (NET) are rare neoplasms arising from diffusive neuroendocrine cells of various organs. Current systemic treatments for advanced or metastatic NET are limited. The clinical effect of VEGFR inhibitors has not been well characterized in extrapancreatic NET. In this phase II study by Xu and colleagues, surufatinib, a novel and selective VEGFR inhibitor, showed potent and durable antitumor activity in patients with well-differentiated advanced NET irrespective of the primary tumor origins; similar antitumor activity was observed in both VEGFR-inhibitor-naïve and pretreated patients. This study provided clinical evidence that surufatinib might be a promising therapeutic candidate for patients with well-differentiated advanced NET.

95% of all peptide vaccines focus on cellular T cell immune responses. Bekaii-Saab and colleagues report a new paradigm in immunotherapy that focuses on humoral responses based on chimeric conformational B-cell epitope vaccines. In the phase 1b trial, the combination of two HER-2 peptide B-cell epitope vaccines engineered to represent the trastuzumab and pertuzumab binding sites was safe, exhibited antitumor activity, and showed preliminary indications that peptide vaccination may avoid therapeutic resistance and offer a promising alternative to monoclonal antibody therapies.

The retinoic acid-related orphan receptor gamma (RORgamma) is a nuclear receptor transcription factor that acts as an immune cell master control switch through regulation of type 17 effector T-cell differentiation and function. In this phase 1 study, Mahalingam and colleagues evaluated the safety, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of LYC-55716, a first in class, oral, selective RORgamma agonist. The study established a recommended dose for further study and provided evidence of clinical activity of LYC-55716. Based on the findings of this study, RORgamma agonists may represent a new approach to enhance antitumor immunity for patients with advanced cancers.

Immunotherapy is used to treat several types of squamous cell carcinomas (SCC), but response rates are relatively low. In this study, Li and colleagues explored the immune landscape of esophageal, head and neck, lung, and cervical SCC. They identified and validated six immune subtypes, each of which was associated with distinct gene expression profiles, genetic aberrations, tumor-infiltrating immune cell composition and functional orientation, cytokine profiles, and clinical outcomes. This study provides a conceptual framework to understand the complex immune microenvironment of SCC and may have implications for the design of combination treatment strategies and selection of patients for immunotherapy.