What We're Reading
Cancer Immunol Res July 1 2020 8 (7) 843-843;
Despite the link of tumor mutational burden with response to immunotherapy, it is not universal across tumor types. In prostate cancer, the burden of tumor gene fusions positively correlates with antitumor immunity, inversely correlating with tumor mutational burden.
Immune-related adverse events (irAEs), and the resulting length of hospitalization and mortality rate, are age specific in patients with melanoma treated with immunotherapy. These differences could be due to specific irAEs that occur in different age groups.
A vaccination approach is presented. This strategy overcomes the main limitation of focusing on tumor mutation–derived neoantigens by vaccinating against neoantigens that are experimentally induced in tumor cells.
Tumor-infiltrating CD8+ T cells from patients with three cancer types exhibit a memory phenotype, a sequential pattern of immune checkpoint expression with additional CD39 expression, and CD28 loss. These cells' effector potential can be unleashed with anti–PD-1.
A triple-therapy combination leads to repolarization of M2 tumor-associated macrophages (TAMs) to M1 TAMs. As a result, this combination therapy elicits robust antitumor responses against primary NSCLC tumors and can also boost antitumor abscopal responses.
ILDR2 is an immune checkpoint expressed by certain stromal lymph node cells called fibroblastic reticular cells. ILDR2 negatively interferes with T-cell activity, and its inhibition by the antibody BAY 1905254 is beneficial in preclinical models.
A subset of CD8+ T cells highly express CD226. The efficacy of anti-TIGIT therapy is more profound on high CD226 expressors rather than low. TIGIT blockade activity depends on CD226 phosphorylation, which predicts the outcome of anti-TIGIT therapy.
Antitumor T-cell grafts with HLA class I, HLA class II, and TCR molecules concurrently ablated evade allogeneic T-cell responses. These cells can be used as a universal T-cell source for adoptive cancer immunotherapy.
Long noncoding RNAs (lncRNAs) could potentially regulate immune checkpoint molecules. The lncRNAs HCP5 and MIAT are upregulated when prognosis is poor. They drive PD-L1 expression and inhibit the efficacy of immune checkpoint blockade.
Antibody blockade of PD-L1 is associated with toxicities, thus new targeting strategies are needed. Verteporfin suppresses PD-L1 expression via Golgi-related autophagy and disruption of STAT1–IRF1–TRIM28 signaling.
The progression of glioblastoma is marked by a proneural-to-mesenchymal transition (PMT) and is associated with radiation resistance. PMT is triggered by the release of microRNA-filled small extracellular vesicles from tumor-associated macrophages that target CHD7 in glioma stem cells.