Masters of Immunology
Thomas A. Waldmann
Cancer Immunol Res March 1 2015 3 (3) 219-227; DOI:10.1158/2326-6066.CIR-15-0009
Hunsucker, McGary, Vincent, and colleagues report that low-frequency, antigen-specific T-cell responses may be specifically tested using tetramer-based, single-cell sorting and sequencing of the antigen-specific TCRβ clonotypes, and then mapping them onto a patient's TCRβ to quantify antigen-driven clonal expansion.
Zippelius and colleagues report that anti-CD40 treatment induces T cell– and IFNγ-dependent PD-L1 expression on tumor-infiltrating monocytes and macrophages. Consequently, the combination of anti-CD40 therapy with PD-1/PD-L1 blockade elicits effective tumor rejection in mouse models of breast and colon cancer.
deLeeuw and colleagues analyzed tumor-infiltrating lymphocytes (TIL) in primary high-grade serous ovarian cancer and discovered a novel subset of CD4+ TIL that are strongly associated with patient survival and hence warrant consideration as effector cells for immunotherapy.
Bastid and colleagues show that CD39 is highly expressed on tumor-infiltrating lymphocytes, tumor stroma, but also on tumor cells; treatment with CD39 inhibitors or blocking antibody alleviated the tumor-induced inhibition of T-cell proliferation and increased CTL- and NK cell–mediated cytotoxicity.
Xu and colleagues describe a novel, fully humanized, aglycosylated bispecific antibody targeting GD2 pentasaccharide with femtomolar cytotoxic EC50 against cancer cell lines that activates T cells in situ, drives intravenous T cells and monocytes to infiltrate tumor stroma, and ablates neuroblastoma and melanoma xenografts.
Sabado, Pavlick, and colleagues show that NY-ESO-1 protein in Montanide with or without topical resiquimod is safe, well-tolerated, and induces antibody and CD4 T-cell responses in most patients, but the addition of topical resiquimod is not sufficient to induce consistent NY-ESO-1–specific CD8 T-cell responses.
Johnson, Lovly, and colleagues performed a retrospective analysis of clinical outcomes following immunotherapy on 229 patients with melanoma with or without NRAS mutations and report that NRAS mutations in advanced melanoma correlate with increased benefit from immune-based therapies compared with other genetic subtypes.
Moskalenko, Pan, and colleagues show in a B16 melanoma model that tumor clearance from the combined regimen of cytotoxic doses of cyclophosphamide and an antibody targeting melanoma differentiation antigen tyrosine-related protein 1 requires Fcγ receptors and innate CD90+NK1.1− lymphocytes, not classical NK cells.