What We're Reading
Cancer Immunol Res July 1 2019 7 (7) 1037-1037;
Favorable response of advanced MM was seen in one patient given CAR T-cell therapy followed by localized radiation therapy. That TCR clonal expansion and CRS-like findings occurred after radiation therapy suggests synergy between these treatment modalities.
Tumor evasion can ensue from too few infiltrating cytotoxic T cells—type 1 (Tc1) or 17 (Tc17)—or infiltration of dysfunctional effectors. RORγ agonists augmented Tc17 survival and lytic activity and directed recruitment of other functional effector cells.
The prognosis for breast cancer and melanoma patients is worse if their tumors metabolically regulate pH, promoting an acidic microenvironment, through enzymes like CAIX. Inhibition of CAIX plus blockade of immune checkpoints boosts antitumor responses by buffering acidosis.
VISTA, induced on MDSCs by hypoxia in the tumor microenvironment, enhances suppression of both CD4+ and CD8+ T cells. This mechanism of hypoxia-driven immune escape and checkpoint resistance suggests a translatable approach to combination therapies.
The density of C1q-producing TAMs and C4d deposits, hallmarks of complement activation, are negative prognostic factors in human clear-cell renal cell carcinoma. Thus, the classical complement pathway is a potential therapeutic target for this cancer.
Blocking BAFF-R early in ALL promotes killing of leukemic cells. However, if given at later disease stages, efficacy is limited due to TGFβ. Combining VAY736 and a TGFβR1 inhibitor improved treatment efficacy in advanced and drug-resistant ALL.
An immune checkpoint blocking antibody was developed against cancer cell surface PCNA, a ligand for NK-cell protein NKp44. Tests of the antibody in mice bearing patient-derived xenografts showed promise for overcoming tumor resistance to immunotherapy.
The YB-1 signaling axis promotes tumor immune evasion and multidrug resistance. When targeted, chemoresistance decreased and antitumor responses were enhanced, suggesting an avenue for treating tumor multidrug resistance and immunosuppressive tumor microenvironments.
Whole exome and RNA sequencing of paired primary and recurrent glioma specimens revealed decreased neoantigen expression at recurrence. Evidence of persistent immune responses suggests immune selection pressure as a possible mechanism, despite treatment with standard, nonimmune-based regimens.
Innate immunity can provide new targets for immunotherapy. Singscore, a gene-set scoring method, revealed that NK cell infiltration correlated with improved patient survival rates. Stromal and tumor elements, as well as cytokines involved in NK function were investigated.
Anti-CCR4 treatment to target regulatory T cells induced clinical responses and prolonged survival in dogs with spontaneous bladder cancer. Expression of CCR4 in human tumor samples suggests translational relevance for treatment of bladder cancer in humans.
Multipotent microparticles bearing T-cell antigens and costimulatory molecules—and containing cytokines, chemokines, and checkpoint inhibitors—were injected intravenously into melanoma-bearing mice. These particles inhibited melanoma growth and expanded tumor-specific CTLs in peripheral blood, spleen, and tumor tissue.
The ability to generate HPV-derived peptide antigens is governed by which ERAP1 molecules are expressed. Thus HPV+ OPSCC patients have different numbers of tumor-infiltrating CD8+ T cells, which affects disease progression.
Thyroid disorders are common immune-related adverse events, and improved clinical management is needed. In this study, high dose glucocorticoids did not improve duration of thyrotoxicosis or onset of hypothyroidism in patients treated with immune checkpoint inhibitors.