Masters of Immunology
Melody A. Swartz
Cancer Immunol Res August 1 2014 2 (8) 701-707; DOI:10.1158/2326-6066.CIR-14-0115
Salazar and colleagues describe an ongoing trial of sequential intratumoral and intramuscular poly-ICLC vaccination, partly based on results in a pilot volunteer patient with advanced rhabdomyosarcoma; the authors postulate conversion of tumor into a personalized vaccine, activating innate and adaptive immunity.
Noonan and colleagues report that addition of the phosphodiesterase-5 inhibitor, tadalafil, reduced the expression of immunosuppressive mediators in myeloid-derived suppressor cells, restored the patient's responsiveness to lenalidomide-based therapy, and elicited a durable antimyeloma clinical response.
Schneiders and colleagues show that phosphoantigen (pAg)-activated Vγ9Vδ2-T cells were able to present glycolipid Ag α-galactosylceramide to iNKT cells not from de novo synthesis of antigen-presenting molecules but from trogocytosed CD1d-containing membrane fragments from pAg-expressing cells.
Müller, Martin, von Bergwelt-Baildon, Zippelius, and colleagues show that the dolastatin family of microtubule inhibitors induced tumor-resident DC maturation and homing to draining lymph nodes to potentiate cellular antitumor immune responses, providing a rationale for combining dolastatin-based treatments with immunotherapy.
Zom, Khan, Britten, and colleagues report that direct conjugation of lipopeptide Pam3CSK4 to synthetic long peptides enhanced in vivo targeting and maturation of the conjugate with superior priming of CD8+ and CD4+ T cells in two mouse tumor models.
Swierczak and colleagues show that blockade of CSF-1R signaling promoted metastasis in two mouse mammary tumor models, with increases in serum G-CSF and neutrophils, which can be overcome by anti–G-CSFR antibodies, raising concerns about targeting CSF-1R as breast cancer therapy.
Ward-Kavanagh and colleagues demonstrate in a mouse model of prostate cancer that radiation conditioning promoted accumulation of granzyme B–expressing donor T cells in lymphoid organs and prostates, altering the tumor microenvironment so that subsequent rounds of T-cell therapy can promote therapeutic benefit.
The Zhang laboratory reports that restored miR-17/20a expression in murine breast and colon cancer cells reprogrammed tumor cells for NK cell–mediated cytotoxicity by inhibiting MHC class I via the Mekk2– Mek5–Erk5 pathway, indicating that miR-17/20a may be a tumor suppressor.
Sierra and colleagues show that myeloid-derived suppressor cells (MDSC) blocked Notch expression in T cells via nitric oxide–dependent mechanisms, and overexpression of the Notch 1 intracellular active domain rendered the CD8+ T cells resistant to the MDSC-induced tolerogenic effect.
Kitano and colleagues developed an algorithm to determine the frequency of monocytic MDSC (m-MDSC), performed a retrospective analysis of samples from patients treated with ipilimumab, and found m-MDSC frequencies inversely correlated with clinical response and CD8+ T-cell expansion following treatment.