What We're Reading
Cancer Immunol Res December 1 2018 6 (12) 1443-1443;
Immunotherapy-induced diarrhea is usually attributed to inflammatory colitis. However, late-onset diarrhea in patients treated with PD-1 inhibitors may be caused by pancreatic atrophy, leading to exocrine insufficiency. Although steroid-resistant, this condition may be treated with oral enzyme supplements.
Melanoma-associated fibroblasts contributed to checkpoint blockade resistance via MMP-9–dependent PD-L1 cleavage and influenced the impact of TGFβ inhibition on responses to anti–PD-1. These findings highlight the importance of understanding immunotherapy effects on the tumor microenvironment.
Cancer-associated stromal cells restrain responses to immunotherapy and are associated with poor prognosis. Isolation of mesenchymal cells from fresh breast tumor samples revealed subsets with distinct phenotype and immunoregulatory potential. These observations may lead to better designed immunotherapies.
Structural and immunogenic differences between HER2 and Δ16HER2 were determined, and DNA and phage-based vaccines were developed. This vaccine strategy led to breaking immune tolerance in a breast cancer model, allowing for improved antitumor responses.
Treatment-resistant tumors were pretreated with an FDA-approved drug, which rendered them responsive to virotherapy. Both viral replication and the immune-mediated antitumor response are integral to the efficacy of this combination therapy.
A screening tool capable of high-throughput identification of compounds and genes affecting antitumor responses is presented. Specific EGFR inhibitors were identified and validated as enhancing T cell–mediated killing of tumor cells, providing a proof-of-principle for this approach.
Influence of T-cell priming on effector antitumor responses was evaluated. Loss of secondary contacts between a peptide non-anchor residue and MHC skews effector functions to favor cytotoxicity over cytokine production in T cells specific for a melanoma self-antigen.
Solid tumors modulate the expression of molecules induced by licensing interactions during NK-cell education and alter their function. Expression of these molecules can predict patient survival and have implications in the design of NK cell-based therapies.
PD-1 expression and function were assessed in NK cells from patients with head and neck cancer. NK cell dysfunction was reversed by PD-1 blockade and improved responses to cetuximab therapy, thus, providing an approach to reverse tumor immune evasion.
The HDAC inhibitor, entiniostat, impairs myeloid immunosuppressive function, and in combination with immune checkpoint inhibitors, improves T-cell responses in models of breast and pancreatic cancers. These data provide rationale for combination therapy in patients to improve antitumor responses.
The Treg/Th17 ratio is altered in epithelial ovarian cancer. Exosomal miRNAs from tumor-associated macrophages contribute to this T-cell imbalance, which promotes an immune suppressive tumor microenvironment and favors progression and metastasis of epithelial ovarian cancer cells.