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Achieving depletion of regulatory T cells while sparing tumor-specific effector T cells has long remained an elusive goal of immunotherapy. A new study describing the development of an antibody to the cytokine receptor CD25 optimized to ensure depletion of regulatory T cells without blocking binding of the cytokine IL-2 will reinvigorate interest in this therapeutic avenue.
As COVID-19 continues to surge, it is essential to understand and address the looming crisis of mental-health issues caused or exacerbated by the pandemic.
The response to immunotherapy has been linked to human leukocyte antigen (HLA) genotype in certain cancers. A new study examining the interaction between cancer type–specific mutational exposures and the B44 and B27 HLA supertypes finds that patients with mutant peptides complementary to these supertypes receive the most benefit from immune-checkpoint blockade.
Beyond the suffering caused by the disease, most patients diagnosed with cancer in the USA face substantial financial hardships associated with their treatments. What underlies the financial toxicity of cancer?
Mehta et al. show that PARP inhibition induces CSF1R-dependent immune-suppressive macrophages, and that its blockade restores PARP inhibitor efficacy and stimulates CD8+ T cell-dependent antitumor immunity in triple-negative breast cancer.
Immunostimulatory agents such as Toll-like receptor (TLR) agonists have shown promising antitumor efficacy but are associated with therapy-related toxicities when delivered systemically. Immune-stimulating antibody conjugates are now shown to deliver TLR agonists with potent preclinical antitumor activities.
Westermann and colleagues define four subtypes of neuroblastoma based on super-enhancer profiles in primary patient samples, which could be linked to distinct clinical outcomes and cell identity characteristics.
Alonso and colleagues develop immune-stimulating antibody conjugates capable of specific delivery of TLR7/8 agonists to tumors, which induces durable antitumor immunity.
Piccolo and colleagues perform integrated single-cell analyses and identify YAP/TAZ regulation of glioma stem cell differentiation as a core dependency for tumor maintenance.
Edelman Saul and colleagues review the challenges and strategies for implementing low-dose computed tomography screening for lung cancer in low- and middle-income countries.
Fan and colleagues report that inhibition of PAK4 normalizes the tumor vascular microenvironment and sensitizes glioblastomas to CAR-T cell immunotherapy.
Invariant natural killer T cells (iNKT cells) are innate-like CD1d-restricted T cells that have NK cell–like properties and bear an invariant T cell receptor (iTCR). iNKT cells have shown potential for cancer immunotherapy. A study now shows that stabilization of the iTCR–CD1d complex via a single-chain bi-specific antibody stimulates iNKT cell–mediated anti-tumor immunity.
Recent advances in cancer neuroscience necessitate the systematic analysis of neural influences in cancer as potential therapeutic targets in oncology. Here we outline recommendations for future preclinical and translational research in this field.
Although RET alterations are relatively frequent across tumor types, specific targeting of RET in the clinic has been challenging. Ambrogio, Aggarwal and colleagues provide their views on how mechanistic studies have swiftly translated into powerful targeted therapies in two recent clinical studies that led to the FDA approval of selpercatinib for certain tumors in which RET is altered.
Beltran and colleagues discuss the challenges in treating metastatic prostate cancer and strategies to accelerate precision oncology and improve therapy and clinical decisions in this setting.
Garon and colleagues demonstrate that the association of HLA supertype B44 with response to immune checkpoint blockade in melanoma but not NSCLC is related to differential mutational features that influence HLA binding of neoepitopes.
Bhardwaj et al. report that adding Flt3 ligand to the treatment strategy effectively increased DC populations and increased T-cell responses in a randomized phase II trial of a DC-targeted vaccine for the melanoma antigen NY-ESO-1.
Samstein et al. report that mutations in BRCA1 and BRCA2 result in distinct mutational genomic landscapes, effects on the tumor-immune microenvironment and response to immune checkpoint therapy.