What We're Reading
Cancer Immunol Res June 1 2020 8 (6) 723-723;
Innate lymphoid cells (ILCs) are strategic players in immune responses. Group 3 ILCs (ILC3s) are found in CRC tissue associated with tertiary lymphoid structures (TLSs). Both TLSs and ILCs decrease during CRC progression, suggesting an unsuspected relationship.
CAR T cells can be driven into a dysfunctional state through excessive costimulation. Understanding the limits of costimulation for CAR T cells will aid design of more efficacious CAR T cells for future clinical trials.
Tumor-directed T cells function better when expressing IL18 rather than IL12. TCR-modified T cells secreting IL18 eradicate established tumors in syngeneic models in combination with sublethal irradiation and in xenograft models, providing evidence to support IL18-boosted T-cell clinical trials.
Donor lymphocyte infusion after allogenic bone marrow transplantation can promote antitumor immunity but risks graft-versus-host disease. If there is no prior marrow transplantation, then donor lymphocyte infusion allows donor NK cells to control MHC-negative melanoma without toxicity.
Tumor cells evade NK-cell–mediated immunity by proteolytic shedding of the activating MICA/B ligands. Use of a MICA/B antibody inhibits MICA/B proteolytic shedding, leading to NK-cell responses against tumor cells resistant to cytotoxic T cells.
Antibody agonists that target T-cell costimulatory pathways are being tested in the clinic. FS120, a dual agonist antibody specific for CD137 and OX40, delays tumor growth by improving the activation and proliferation of peripheral T cells.
Improving the in vivo persistence of adoptive cell therapies correlates to better patient responses. Histone deacetylase inhibitors and IL21 shift CD8+ T cells to a more persistent, central memory phenotype by increasing CD28 promoter accessibility.
Amplification of tumor hypoxia by anti-VEGF treatment enhances CD8+ T-cell antitumor responses through increased HIF1α activity. Combining anti-angiogenics and immunotherapeutics may be useful for the treatment of cancer.
A substantial proportion of cells with early-stage myeloid-derived suppressor cell (e-MDSC) surface markers in circulation and in ascites of patients with ovarian cancer are basophils. Exclusion of basophils from e-MDSC is required for prognostic and therapeutic studies.
CSF1R promotes efficient Langerhans cell (LC) differentiation from hematopoietic progenitors and migration, which may be reduced by CSF1R kinase inhibition. CSF1R expression in clinical LC histiocytosis (LCH) specimens suggests potential for CSF1R blockade in the treatment of LCH.