The efficacy of PD-1/L1 checkpoint blockade in cancer patients is limited by inadequate T-cell invigoration. Buchan and colleagues report synergism between PD-1/L1 blockade and anti-CD27 mAb for CD8+ T-cell activation and tumor therapy in multiple models, including in human CD27 transgenic mice. They find that combination therapy triggers a convergent program largely dependent on synergistic IL-2 signalling and Myc, but a division of labor such that PD-1/L1 blockade promotes a cytotoxic gene-expression profile, whereas anti-CD27 preferentially drives proliferation. These data provide a mechanistic basis for pursuing the combination of checkpoint blockade and anti-CD27 in the clinic.The central nervous system (CNS) is a sanctuary site from targeted drugs. While the multiple kinase inhibitor, entrectinib, is effective in the treatment of NTRK1-fusion positive cancers with CNS metastasis, resistance usually develops. Nishiyama and colleagues found that the NTRK1-G667C mutation, which induces moderate resistance to entrectinib, caused acquired entrectinib resistance of brain metastasis. Importantly, foretinib inhibited TRK-A with G667C mutation and overcame entrectinib resistance in the liver and brain metastasis models. These findings provide a rationale for clinical trials with foretinib in cancer patients with entrectinib-resistant tumors harboring the NTRK1-G667C mutation, including patients with brain metastases.Preoperative chemotherapy is used in certain groups of breast cancer patients, but many patients do not respond and/or suffer disease progression after treatment. Liu and colleagues show that cytotoxic chemotherapy induces monocytosis in the bone marrow, resulting in increased blood levels of monocyte chemoattractant proteins, which stimulate the cancer stem-like cell phenotype to promote tumor malignancy. The study suggests that pharmacologic inhibition of CCR2 may serve as a potential cotreatment during conventional chemotherapy to target therapy-induced cancer stemness.The prognostic value of the androgen receptor (AR) in breast cancer is controversial, due in part to differences in cohorts and methodology, including the cut-point used for AR positivity. To resolve this controversy, Ricciardelli and colleagues assessed AR positivity in two independent primary breast cancer cohorts and determined the optimal cut-point by ROC analysis. An AR cut-point of 78% positivity, approximating the median staining, provided optimal sensitivity and specificity to predict breast cancer survival. Testing this cut-point in prospective cohorts is now warranted for clinical implementation of AR as a prognostic factor in the management of breast cancer.