Volume 1 Issue 12, December 2020

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.

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.

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?

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.

Quezada and colleagues develop improved anti-CD25 antibodies that preserve IL-2 signaling and enhance single-agent antitumor immunity and immunotherapy through specific and efficient T_reg cell depletion.

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.

Jordan and colleagues show the role of increased fatty acid metabolism in AML stem cells, in both intrinsic and acquired resistance to combination venetoclax and azacitidine, and find that cells can be re-sensitized by inhibiting fatty acid oxidation.

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.

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.