Coinfection with Human Cytomegalovirus Genetic Variants in Transplant Recipients and Its Impact on Antiviral T Cell Immune Reconstitution.
Journal of Virology 90(16):7497 (2016)
Reconstitution of T cell immunity is absolutely critical for the effective control of virus-associated infectious complications in hematopoietic stem cell transplant (HSCT) recipients. Coinfection with genetic variants of human cytomegalovirus (CMV) in transplant recipients has been linked to cl...
Checkpoint Immunotherapy: Picking a Winner.
Cancer Discovery 6(8):818 (2016)
Robust biomarkers of response that predict which patients will or will not respond to immune checkpoint blockade need to be identified. New data suggest that the presence of an adaptive immune signature in the tumor biopsies of patients with melanoma early on therapy compared to pretreatment can...
Adenosine 2B Receptor Expression on Cancer Cells Promotes Metastasis.
Cancer Research 76(15):4372 (2016)
Adenosine plays an important role in inflammation and tumor development, progression, and responses to therapy. We show that an adenosine 2B receptor inhibitor (A2BRi) decreases both experimental and spontaneous metastasis and combines with chemotherapy or immune checkpoint inhibitors in mouse m...
Harnessing the immune system in acute myeloid leukaemia.
Critical Reviews in Oncology/Hematology 103:62 (2016)
Acute myeloid leukaemia (AML) is an aggressive blood cancer caused by the proliferation of immature myeloid cells. The genetic abnormalities underlying AML affect signal transduction pathways, transcription factors and epigenetic modifiers. In solid tumours, it is emerging that the genetic lands...
CIS is a potent checkpoint in NK cell-mediated tumor immunity.
Nature Immunology 17(7):816 (2016)
The detection of aberrant cells by natural killer (NK) cells is controlled by the integration of signals from activating and inhibitory ligands and from cytokines such as IL-15. We identified cytokine-inducible SH2-containing protein (CIS, encoded by Cish) as a critical negative regulator of IL-...
Combination Anti-CTLA-4 and Anti-RANKL in Metastatic Melanoma.
Journal of Clinical Oncology 34(12):e104 (2016)
Suppression of Metastases Using a New Lymphocyte Checkpoint Target for Cancer Immunotherapy.
Cancer Discovery 6(4):446 (2016)
CD96 has recently been shown as a negative regulator of mouse natural killer (NK)-cell activity, with Cd96(-/-)mice displaying hyperresponsive NK cells upon immune challenge. In this study, we have demonstrated that blocking CD96 with a monoclonal antibody inhibited experimental metastases in th...
Immune responses in multiple myeloma: role of the natural immune surveillance and potential of immunotherapies.
Experientia. Basel 73(8):1569 (2016)
Multiple myeloma (MM) is a tumor of terminally differentiated B cells that arises in the bone marrow. Immune interactions appear as key determinants of MM progression. While myeloid cells foster myeloma-promoting inflammation, Natural Killer cells and T lymphocytes mediate protective anti-myelom...
Clinical relevance of host immunity in breast cancer: from TILs to the clinic.
Nature Reviews Clinical Oncology 13(4):228 (2016)
The clinical relevance of the host immune system in breast cancer has long been unexplored. Studies developed over the past decade have highlighted the biological heterogeneity of breast cancer, prompting researchers to investigate whether the role of the immune system in this malignancy is simi...
Combination cancer immunotherapies tailored to the tumour microenvironment.
Nature Reviews Clinical Oncology 13(3):143 (2016)
Evidence suggests that cancer immunotherapy will be a major part of the combination treatment plan for many patients with many cancer types in the near future. There are many types of immune processes involving different antitumour and tumour-promoting leucocytes, and tumour cells use many strat...
TGF-β inhibits the activation and functions of NK cells by repressing the mTOR pathway.
Science Signaling 9(415):ra19 (2016)
Transforming growth factor-β (TGF-β) is a major immunosuppressive cytokine that maintains immune homeostasis and prevents autoimmunity through its antiproliferative and anti-inflammatory properties in various immune cell types. We provide genetic, pharmacologic, and biochemical evidence that a c...
Correction: Blimp-1-Dependent IL-10 Production by Tr1 Cells Regulates TNF-Mediated Tissue Pathology.
PLoS Pathogens 12(2):e1005460 (2016)
Acquired resistance to immunotherapy and future challenges.
Nature Reviews: Cancer 16(2):121 (2016)
Advances in immunotherapy have resulted in remarkable clinical responses in some patients. However, one of the biggest challenges in cancer therapeutics is the development of resistant disease and disease progression on or after therapy. Given that many patients have now received various types o...
The Helix-Loop-Helix Protein ID2 Governs NK Cell Fate by Tuning Their Sensitivity to Interleukin-15.
Immunity 44(1):103 (2016)
The inhibitor of DNA binding 2 (Id2) is essential for natural killer (NK) cell development with its canonical role being to antagonize E-protein function and alternate lineage fate. Here we have identified a key role for Id2 in regulating interleukin-15 (IL-15) receptor signaling and homeostasis...
Improved Treatment of Breast Cancer with Anti-HER2 Therapy Requires Interleukin-21 Signaling in CD8+ T Cells.
Cancer Research 76(2):264 (2016)
The HER2/ErbB2 monoclonal antibody (mAb) trastuzumab is combined with chemotherapy as a standard-of-care for newly diagnosed HER2(+) breast cancer patients, but some patients treated with this combination therapy experience early relapse. Our analysis of data from a clinical trial evaluating the...
Transforming growth factor-β and Notch ligands act as opposing environmental cues in regulating the plasticity of type 3 innate lymphoid cells.
Science Signaling 9(426):ra46 (2016)
Group 3 innate lymphoid cells (ILC3s) are composed of subsets that are either positive or negative for the natural cytotoxicity receptor (NCR) NKp46 (encoded by Ncr1). ILC3s are located at mucosal sites, such as in the intestine and lung, where they are exposed to billions of commensal microbes ...
Host immunity contributes to the anti-melanoma activity of BRAF inhibitors.
Journal of Clinical Investigation 126(1):402 (2016)
Mouse Models of Tumor Immunotherapy.
Advances in Immunology 130:1 (2016)
Immunotherapy is now evolving into a major therapeutic option for cancer patients. Such clinical advances also promote massive interest in the search for novel immunotherapy targets, and to understand the mechanism of action of current drugs. It is projected that a series of novel immunotherapy ...
NK Cells and Cancer Immunoediting.
Current Topics in Microbiology and Immunology 395:115 (2016)
Natural killer (NK) cells are innate lymphoid cells (ILC) known for their ability to recognize and rapidly eliminate infected or transformed cells. Consequently, NK cells are fundamental for host protection against virus infections and malignancies. Even though the critical role of NK cells in c...
Blimp-1-Dependent IL-10 Production by Tr1 Cells Regulates TNF-Mediated Tissue Pathology.
PLoS Pathogens 12(1):e1005398 (2016)
Tumor necrosis factor (TNF) is critical for controlling many intracellular infections, but can also contribute to inflammation. It can promote the destruction of important cell populations and trigger dramatic tissue remodeling following establishment of chronic disease. Therefore, a better unde...