Highlights of This Issue

Abstract

The efficacy of rituximab and ofatumumab in non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL) depends in part on the induction of complement-dependent cytotoxicity (CDC). Upregulation of CD59, a critical CDC inhibitor, is an important determinant of sensitivity to rituximab treatment. Ge and colleagues document that rILYd4, a potent human CD59 inhibitor, enhances the CDC effects of ofatumumab or rituximab on rituximab-resistant NHL cell lines and primary CLL cells. These effects correlated negatively with CD59 levels. Therefore, rILYd4 may be a new approach to enhancing the anticancer activity of ofatumumab or rituximab in relapsed NHL or CLL.Merkel cell carcinoma (MCC) is an aggressive skin cancer with limited treatment options for progressive disease. The Merkel cell polyomavirus (MCPyV) is integrated into most MCC tumors, and it encodes oncoproteins required for ongoing tumor growth. Iyer and colleagues identified MCPyV-specific CD8 and CD4 T-cell responses from MCC tumors and blood. The 26 novel MCPyV epitopes identified in this report will facilitate isolation of tumor-specific T lymphocytes, further characterization of immune evasion mechanisms used by this cancer, and development of MCPyV-specific immunotherapy for Merkel cell carcinoma.Brunsvig and colleagues report on 2 trials evaluating immunotherapy with the telomerase peptide GV1001 in patients with non-small cell lung cancer. In a phase I-II study, a GV1001-specific immune response was detected in 13 of 24 subjects (54%) after vaccine monotherapy. In a second trial, adjuvant vaccination after chemoradiotherapy produced an 80% immune response rate. The vaccine treatment was well tolerated. Immune responders recorded increased survival compared with nonresponders. Long-term survivors developed durable T-cell memory responses with IFN-γhigh/interleukin (IL)-10low/IL-4low cytokine profiles. These findings support the concept of combining vaccination with chemoradiotherapy and warrant a randomized trial evaluating GV1001 in patients with non-small cell lung cancer.Germline variants in cancer stem cell (CSC) genes have recently been linked to cancer outcome and chemoresistance. Gerger and colleagues investigated germline polymorphisms in a comprehensive panel of colon CSC gene variants to predict time to tumor recurrence in patients with stage III and high-risk stage II colon cancer treated with 5-fluorouracil-based adjuvant chemotherapy. Common gene variants in CD44, ALCAM, and LGR5 were significantly associated with time to tumor recurrence, and a specific gene variant profile represented a high-risk subgroup, indicating valuable prognostic biomarkers in colon cancer patients and a molecular characterization of stem cells to develop more successful treatment strategies in the future.