Masters of Immunology
Michael L. Dustin
Cancer Immunol Res November 1 2014 2 (11) 1023-1033; DOI:10.1158/2326-6066.CIR-14-0161
Steinberg and colleagues show that the BRAF-inhibitor PLX4720 enhanced intratumoral Treg apoptosis and decreased both the proportion and the per-cell immunosuppressive function of MDSCs, thus informing the design of combinatorial therapies for melanoma.
Bajor and colleagues used next-generation sequencing of TCRs in the tumor and blood to identify the emergence and persistence of a de novo T-cell repertoire following agonistic CD40 therapy, highlighting the potential of immune agonists in therapy and TCR deep sequencing in immune assessment.
Singh and colleagues show that RNA-CAR T cells mediate rapid and long-term tumor destruction when delivered locally but not when delivered systemically due to the inability of RNA-CAR T cells to penetrate the tumor microenvironment.
Paulson and colleagues report that 84% of Merkel cell carcinoma (MCC) tumors downregulated MHC-I expression, and MCC patients treated with intralesional IFNs had increased MHC-I expression on their tumor cells, thus promoting the use of immune-stimulating therapies for MCC.
Abu-Eid, Samara, and colleagues used PI3K–Akt pathway inhibitors to selectively disrupt homeostasis of immunosuppressive Tregs in naïve and tumor-bearing mice, and to enhance vaccine-induced antitumor immune responses, highlighting the therapeutic potential of these inhibitors as Treg-depleting reagents.
Farsaci, Donahue, and colleagues show that combining antiangiogenic tyrosine kinase inhibitors with vaccines increased tumor-infiltrating lymphocytes, decreased tumor density, and enhanced tumor oxygenation, indicating the potential of altering tumor architecture in cancer therapy.
Surana and colleagues report that neutralizing IL4 altered the tumor microenvironment (TME) and enhanced the efficacy of the HER2-directed antibody trastuzumab, thus providing a rationale for targeting soluble mediators in the TME to enhance antitumor antibody therapy.
Nelles and colleagues show in a murine model of leukemia that each of the cytokines IL12, IFNγ, and MCP-1 has a role in guiding a cellular cascade of contactdependent cooperation of NKT cells and DCs that leads to activation of CD4+ cytotoxic T cells and elimination of leukemia.