Regression of glioblastoma after chimeric antigen receptor T-cell therapy
CAR T cells have had great success against hematological cancers but thus far limited activity with solid tumors. In this case study, CAR T cells targeting IL13Rα2 on glioma cells administered both intracranially and intraventricularly reduced metastatic glioma to undetectable levels for an extended period of time.
Systemic immunity is required for effective cancer immunotherapy
As antitumor immune responses are deciphered, data have amassed that describe in great detail what transpires in the tumor itself. However, using a systems-wide assessment, it was found that tumor eradication depends upon an organism-wide coordinated immune response.
Tumor aneuploidy correlates with markers of immune evasion and with reduced response to immunotherapy
The relationship between a tumor's state of aneuploidy and the immune response it elicits or evades is not well understood. Focal, localized aneuploidy was closely associated with tumor cell proliferation, whereas whole arm/chromosome changes produced dosage effects leading to reduced T-cell infiltration. High aneuploidy correlated with poor response to anti–CTLA-4 treatment, and the combination of aneuploidy score and mutational load was a better predictor of survival than either biomarker alone.
The EGR2 targets LAG-3 and 4-1BB describe and regulate dysfunctional antigen-specific CD8+ T cells in the tumor microenvironment
Although CD8+ T cells are often within or near tumors, they can quickly become dysfunctional. This can include expression of EGR2, which drives 4-1BB and LAG-3 expression. These two proteins were found to mark dysfunctional intratumoral T cells that had skewed functional phenotypes. Treatment with a mAb that stimulates 4-1BB plus one that blocks LAG-3 synergistically restored strong antitumor activity and TIL function.
Integrated genomic and molecular characterization of cervical cancer
Cervical cancer is the leading cause of death from gynecological cancers. An extensive genomic, RNA, epigenetic, histologic, protein, and clinical analysis of 228 primary cervical cancers revealed not only distinct mutations and molecular pathways associated with different HPV and histologic/molecular types, but also identified associated potential therapeutic targets.
SATB1 expression governs epigenetic repression of PD-1 in tumor-reactive T cells
PD-1 expression is tightly controlled in T cells. SATB1, a chromatin organizer, prevented premature PD-1 expression and exhaustion by recruiting a deacetylase, NuRD, to regulatory regions of the Pdcd1 gene to reduce transcription. TGFβ was found to inhibit both production of SATB1 and the binding of SATB1 to the Pdcd1 promoter, encouraging PD-1 expression and exhaustion. Thus, dysregulation of SATB1 can diminish antitumor immunity.
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