What We're Reading
Cancer Immunol Res January 1 2019 7 (1) 1-1;
Ipilimumab induced autoantibodies in a fifth of melanoma patients. Patients who developed autoantibodies, especially thyroid autoantibodies, experienced more irAEs and had a survival and response benefit, suggesting that breaking of B-cell tolerance could indicate therapy toxicity and efficacy.
Plasmacytoid dendritic cells (PDCs) can regulate anti-cancer immune responses. Factors in the melanoma secretome drive the PDC compartment to collapse during disease progression, and rescue of PDCs could aid existing spontaneous and drug-induced adaptive immune responses.
In addition to stabilizing cDC1 dendritic cell lineage commitment, BATF3 controls a set of genes required for cDC1 cells to promote tumor rejection. These BATF3-controlled genes, which are independent of cross-presentation, may be targets in the development of immunotherapies.
Adoptive cellular therapy (ACT) with a low-affinity T-cell receptor (TCR) that recognizes a self-antigen yields antitumor cytotoxicity but not autoimmune damage. A better understanding of TCR affinity could ultimately minimize autoimmunity while increasing ACT therapeutic efficacy.
Using a rapid, high-throughput method, peptide/HLA thermal stability was determined for a variety of peptides and peptide variants. This approach allows for predicting neoantigens that can best serve as targets for a robust T-cell response against cancer.
Unconventional spliced peptides can be presented by cancer cells. This survey of peptide characteristics in the immunopeptidome of colon and breast carcinoma cell lines may help to predict and identify an unforeseen pool of antigenic targets for immunotherapy.
Analysis of TCR repertoire clonality in blood samples collected from patients with melanoma before treatment may predict their eventual response to anti-PD1 and anti-CTLA4 therapy. Such a biomarker could help clinicians refine treatment courses for melanoma patients.
An analysis toolkit was developed for characterizing immunological changes over time in clinical samples. Use of this toolkit revealed the presence of a double-negative T-cell subset in melanoma, glioblastoma, and renal cell carcinoma but not in healthy tissues.
NKG2D-CAR T-cell therapy is safe and feasible. Infused cells were transiently detected and exhibited in vitro responses to autologous tumors. However, objective responses to low doses were only seen in lymphodepleted patients, warranting studies to improve efficacy.
Tumor-associated MUC1 is a target for the development of breast cancer vaccines due to its tumor-specific overexpression and aberrant glycosylation. Immunization with synthetically produced tumor-associated MUC1 glycopeptides conjugated to tetanus toxoid resulted in reduced tumor burden in mice.
T-cell numbers and effector functions are diminished by calnexin, an ER chaperone protein, possibly through PD-1 upregulation, in OSCC patients and in a mouse melanoma model. These results suggest calnexin could be targeted to improve immunotherapy responses.
PARP1-mediated poly(ADP-ribosyl)ation of STAT3 drives its dephosphorylation, leading to the inhibition of PD-L1 transcription across multiple cancer types. In patients, PARP1 and PD-L1 expression are inversely correlated. These data highlight a conserved regulatory mechanism for PD-L1 expression.
PD-L1 microSPECT/CT is a technique to detect PD-L1 expression in syngeneic murine models and humanized mice, allowing the monitoring of therapy-induced changes in tumor PD-L1 expression. In the future, this technique could enable patient selection for PD-1/PD-L1-targeted therapies.