Masters of Immunology
Rosanna M. McEwen-Smith, Mariolina Salio and Vincenzo Cerundolo
Cancer Immunol Res May 1 2015 3 (5) 425-435; DOI:10.1158/2326-6066.CIR-15-0062
Quetglas and colleagues report that intratumoral injection of cytolytic nonreplicative Semliki Forest virus vector expressing IL12, along with systemic administration of anti-PD-1/PD-L1 antibodies, induced regression of both virally injected and distal tumors and synergistically prolonged survival in mouse tumor models.
Datta, Xu, and colleagues show that IFNγ/TNFα and anti-HER2 antibody cooperate to restore MHC class I expression on HER2-overexpressing cancer cells, facilitating their recognition and lysis by CD8+ T cells, and suggest that such combinations may be used for optimal HER2-directed CD8+ T-cell immunotherapy.
Johnson and colleagues performed a retrospective analysis of the medical records of 33 melanoma patients who survived more than 2 years after receiving ipilimumab for metastatic disease or as an adjuvant therapy, and report the long-term health outcomes, chronic side effects, and functional status of these patients.
Liadi, Singh, and colleagues used Timelapse Imaging Microscopy In Nanowell Grids (TIMING) to show that CD4+ CD19-chimeric antigen receptor (CAR+) T cells participate in multikilling of tumor cells with slower kinetics of killing than CD8+CAR+ T cells, but high motility subgroups of both T-cell subsets have similar kinetics.
Davenport, Jenkins, and colleagues used time-lapse microscopy and CD8+ T cells coexpressing TCRs and CARs for different antigens to show that CAR T cells can kill multiple tumor cells; engagement via CAR or TCR did not affect killing kinetics; T cells detached faster when CAR was engaged; and CARs are downregulated over time.
Sluijter and colleagues report that intradermal injection of combined CpG/GM-CSF at the primary melanoma excision site prior to removal of sentinel lymph nodes (SLN) led to recruitment of BDCA3+ conventional dendritic cell (cDC) precursors from blood and enhanced DC maturation with selective increase of SLN-resident CLEC9A/BDCA3/CD141+ cDCs.
Beavis, Milenkovski, and colleagues reveal that adenosine receptor blockade enhanced anti-PD-1 efficacy against CD73+ tumors in twomouse models via augmentation of tumor-infiltrating CD8+ T-cell effector function by increasing IFNγ and Granzyme B production and suggest CD73 expression as a biomarker for anti-PD-1 efficacy.
Shiao and colleagues report that inhibiting either macrophage recruitment by CSF-1/CSF-1R-blockade, or macrophage polarization by IL4/13 neutralization, delayed tumor regrowth after radiotherapy or chemotherapy, demonstrating that macrophage antagonists improve responses to cytotoxic therapies.
Triplett, Tucker, and colleagues show that combination cancer therapy using an OX40 agonist and TGFβ receptor blockade depends in part on STAT3 signaling by OX40-expressing T cells; this combination increases intratumoral CD4 and CD8 T-cell functions, which are dampened in the absence of STAT3 signaling.
Qiu and colleagues used cytomegalovirus (CMV)-based prophylactic and therapeutic vaccines expressing foreign or modified self-tumor antigens in a B16 lung metastatic melanoma model and show that these vaccines induced protective antitumor CD8+ T-cell responses even in the presence of preexisting anti-CMV immunity.
Schliemann and colleagues report the use of immunocytokine F16-IL2 in combination with low-dose cytarabine in four patients with relapsed AML after allogeneic hematopoietic stem-cell transplantation; antibody-mediated delivery of IL2 to the AML stroma can activate immune effector cells in the bone marrow of patients.
Medina-Echeverz and colleagues show that agonistic anti-CD40 activates tumor-induced CD80+ and CD40+ hepatic myeloid-derived suppressor cells (MDSC), which cause ROS-mediated hepatotoxicity; these results are recapitulated in human CD14+HLA−DRlow MDSCs, which lose arginase expression and suppressor function in vitro.
Taylor and colleagues studied patients with recurrent or metastatic squamous cell carcinoma of the head and neck treated with cetuximab and lenalidomide and report that enhanced ex vivo antibody-dependent cellular cytotoxicity and innate immunity best predicted clinical responses.