What We're Reading
Cancer Immunol Res September 2 2016 4 (9) 717-717; DOI:10.1158/2326-6066.CIR-16-0WWR
A review of Love and Science: A Memoir by Jan Vilcek, Seven Stories Press, 2016
Tumor cell–intrinsic metabolic factors, a hallmark of kidney cancer, may contribute to anti–PD-1 treatment resistance. This intersection between cancer immunology and metabolism supports an emerging theme of discovery for tumor type–specific biomarkers for immune checkpoint blocking therapies.
Effective adoptive T-cell therapy requires multiple tumor-epitope reactive T-cell clones. Fresh TILs were found to frequently contain such cells. Their TCRs were rapidly isolated based only on their frequency and could be used for personalized TCR-gene therapy.
Too few patients benefit from immune checkpoint inhibition alone. However, patients with melanoma receiving systemic anti-CTLA-4 plus localized treatments had significantly prolonged overall survival. In a multivariate analysis, adding local treatment was an independent factor for improved survival.
Refined subsets of peripheral blood immune cells were assessed prior to therapy in two clinical trials. The resultant “peripheral immunoscores,” compiled through methodology potentially generalizable to other trials, were correlated with clinical benefit in patients receiving vaccine therapy.
Local anticancer therapies can increase antitumor efficacy while reducing toxicities. Cellular vaccines that locally secreted costimulation ligands produced stronger, more specific T-cell activation and tumor rejection with lower ligand concentrations than did vaccines combined with systemic antibody agonists.
B7-H1 suppresses T cells by binding to PD-1, but it is unclear how binding to B7-H1 on cancer cells affects tumors. “Reverse signaling” of B7-H1 on myeloma cells was found to induce drug resistance through the Akt-signaling pathway.
Tumor mutations create neoantigens that increase their immunogenicity but also enable new avenues of immune escape. DomainXplorer analyzes distributions of mutations in cancer genomes searching for correlations with immune response that are not seen by gene level methods.
Tumor-infiltrating CD8+ T cells were profoundly resistant to IL15 complexes, so could not induce tumor regression. Their gene-expression signature was compared with that of productive cytotoxic responses and known differentiation states to determine how to restore antitumor function and cytokine responsiveness.