Masters of Immunology
Lewis L. Lanier
Cancer Immunol Res June 1 2015 3 (6) 575-582; DOI:10.1158/2326-6066.CIR-15-0098
Conry and colleagues report two novel immune-related adverse events—encephalopathy with a reversible splenial lesion and neurogenic bladder—in a patient with stage IV melanoma treated with ipilimumab, which were resolved completely with high-dose methylprednisolone.
Bradley, Chen, and colleagues show that BRAFV600E-induced internalization of MHC class I and its sequestration within endolysosomal compartments can be reversed by MAP kinase inhibitors, demonstrating a direct link between oncogenic activation of the MAPK pathway and MHC class I trafficking and localization.
Park, Dong, and colleagues show in mouse models of melanoma and renal cell carcinoma that stereotactic ablative radiotherapy synergized with PD-1 blockade to induce near-complete regression of the irradiated tumors, and a tumor-specific 66% reduction in the nonirradiated tumors outside the radiation field.
Severson and colleagues show that exhaustion of PD-1+ T cells in tumor-involved lymph nodes from patients with metastatic differentiated thyroid cancer was not complete. While PD-1+CD8+ T cells were variably dysfunctional in their ability to produce cytokines, their proliferative capacity was maintained, and PD-1+CD4+ T cells remained functional.
Ueha, Yokochi, Ishiwata, and colleagues show in three mouse tumor models that CD4 depletion led to tumor-specific CTL proliferation in the draining lymph node and increased tumor infiltration of PD-1+CD8+ T cells; it also synergized with PD-1/PD-L1 blockade to suppress tumor growth and prolong survival.
Ba, Meng, Gostissa, and colleagues developed an ES cell/RAG2-deficient blastocyst complementation-based model for Epstein–Barr virus protein LMP1-driven B-cell lymphomas that allows rapid analyses of genetic alterations that cooperate with LMP1 to promote lymphomagenesis and immunotherapeutic strategies.
Hansmann and colleagues used cytometry by time-of-flight (CyTOF) and next-generation sequencing to detect cancer-associated immune phenotypes in human peripheral blood on a single-cell level, leading to identification of an expanded novel memory B-cell phenotype in multiple myeloma.
Cantor and colleagues created an α4(S988A) integrin-bearing mouse, which precludes PKA-mediated α4 phosphorylation, and showed that manipulating the signaling properties of α4 integrins can selectively enhance T-cell entry, but not myeloid-cell entry, into B16 melanomas, thereby limiting tumor growth.
Zhang and colleagues transduced c-Myc into mouse iPSC (induced pluripotent stem cells) to generate proliferating myeloid cells that propagate in a cytokine-dependent manner while retaining their potential to differentiate into functional antigen-presenting cells that stimulate tumor antigen-specific T-cell responses.
Salimu and colleagues show that preexisting tumor antigen-specific T cells can be reactivated as a consequence of radiotherapy and demonstrate the crucial role that Hsp70, rather than TLR4, plays in antigen cross-presentation from irradiated tumor cells.
Evans and colleagues describe a novel immunomodulatory function of semaphorin 4D (SEMA4D) and show that blocking SEMA4D enhances immune infiltration into tumor and increases antitumor activity in synergy with other immunomodulatory therapies.