Pyroptosis,an inflammatory form of programmed cell death,eliminates a niche where pathogens replicate,providing overall benefits to a host.When left uncontrolled,pyroptosis can lead to severe pathology.Overactive pyro...Pyroptosis,an inflammatory form of programmed cell death,eliminates a niche where pathogens replicate,providing overall benefits to a host.When left uncontrolled,pyroptosis can lead to severe pathology.Overactive pyroptotic activation has been implicated in neuroinflammation,cardiovascular disease,acute respiratory distress syndrome(ARDS),and many other diseases[1,2,3].Because of its multiple and permanent consequences,pyroptosis is a highly regulated signaling pathway.Major regulators of pyroptosis are NLR inflammasomes,which are activated by various“danger”signals such as ATP.展开更多
Chronic inflammatory responses have long been observed to be associated with various types of cancer and play decisive roles at different stages of cancer development. Inflammasomes, which are potent induc- ers of int...Chronic inflammatory responses have long been observed to be associated with various types of cancer and play decisive roles at different stages of cancer development. Inflammasomes, which are potent induc- ers of interleukin （IL）-I~ and IL-18 during infammation, are large protein complexes typically consisting of a Nod-like receptor （NLR）, the adapter protein ASC, and Caspase-1. During malignant transformation or cancer therapy, the inflammasomes are postulated to become activated in response to danger signals arising from the tumors or from therapy-induced damage to the tumor or healthy tissue. The activation of inflammasomes plays diverse and sometimes contrasting roles in cancer promotion and therapy depending on the specific con- text. Here we summarize the role of different inflamma- some complexes in cancer progression and therapy. Inflammasome components and pathways may provide novel targets to treat certain types of cancer; however, using such agents should be cautiously evaluated due to the complex roles that inflammasomes and pro- inflammatory cytokines play in immunity.展开更多
Psoriasis is a chronic inflammatory skin condition that has a fairly wide range of clinical presentations.Plaque psoriasis,which is the most common manifestation of psoriasis,is located on one end of the spectrum,domi...Psoriasis is a chronic inflammatory skin condition that has a fairly wide range of clinical presentations.Plaque psoriasis,which is the most common manifestation of psoriasis,is located on one end of the spectrum,dominated by adaptive immune responses,whereas the rarer pustular psoriasis lies on the opposite end,dominated by innate and autoinflammatory immune responses.In recent years,genetic studies have identified six genetic variants that predispose to pustular psoriasis,and these have highlighted the role of IL-36 cytokines as central to pustular psoriasis pathogenesis.In this review,we discuss the presentation and clinical subtypes of pustular psoriasis,contribution of genetic predisposing variants,critical role of the IL-36 family of cytokines in disease pathophysiology,and treatment perspectives for pustular psoriasis.We further outline the application of appropriate mouse models for the study of pustular psoriasis and address the outstanding questions and issues related to our understanding of the mechanisms involved in pustular psoriasis.展开更多
While immunotherapy has had an important impact on cancer treatment,only approximately a quarter of patients respond to these treatments.Why does it work in some patients but not in other patients?How can we improve t...While immunotherapy has had an important impact on cancer treatment,only approximately a quarter of patients respond to these treatments.Why does it work in some patients but not in other patients?How can we improve the therapeutic efficacy of current immunotherapy?Are there potential new strategies to tackle this problem?The answers to these questions may rely on our in-depth understanding of the basic mechanisms of the cancer immune response,immunotherapeutic efficacy,and resistance.展开更多
Development of alternatively activated （M2） macrophage phenotypes is a complex process that is coordinately regulated by a plethora of pathways and factors. Here, we report that RBP-J, a DNA-binding protein that int...Development of alternatively activated （M2） macrophage phenotypes is a complex process that is coordinately regulated by a plethora of pathways and factors. Here, we report that RBP-J, a DNA-binding protein that integrates signals from multiple pathways including the Notch pathway, is critically involved in polarization of M2 macrophages. Mice deficient in RBP-J in the myeloid compartment exhibited impaired M2 phenotypes in vivo in a chitin-induced model of M2 polarization. Consistent with the in vivo findings, M2 polarization was partially compromised in vitro in Rbpj-deficient macrophages as demonstrated by reduced expression of a subset of M2 effector molecules including arginase 1. Functionally, myeloid Rbpj deficiency impaired M2 effector functions including recruitment of eosinophils and suppression of T cell proliferation. Collectively, we have identified RBP- Jas an essential regulator of differentiation and function of alternatively activated macrophages.展开更多
The majority of colorectal cancer patients are not responsive to immune checkpoint blockade(ICB).The interferon gamma(IFNγ)signaling pathway drives spontaneous and ICB-induced antitumor immunity.In this review,we sum...The majority of colorectal cancer patients are not responsive to immune checkpoint blockade(ICB).The interferon gamma(IFNγ)signaling pathway drives spontaneous and ICB-induced antitumor immunity.In this review,we summarize recent advances in the epigenetic,genetic,and functional integrity of the IFNγsignaling pathway in the colorectal cancer microenvironment and its immunological relevance in the therapeutic efficacy of and resistance to ICB.Moreover,we discuss how to target IFNγsignaling to inform novel clinical trials to treat patients with colorectal cancer.展开更多
Cancer immunotherapy,including immune checkpoint blockade and CAR-T cell therapy,has introduced revolutionary approaches to treating patients with cancer.The success and hope of cancer immunotherapy have continuously ...Cancer immunotherapy,including immune checkpoint blockade and CAR-T cell therapy,has introduced revolutionary approaches to treating patients with cancer.The success and hope of cancer immunotherapy have continuously stimulated high interest in dissecting immunotherapy resistance mechanisms,researching previously unknown therapeutic targets,and informing novel clinical trials in cancer therapy.The notion that the tumor microenvironment holds the key to understanding tumor immunity and developing novel immunotherapy has been well established in the field of tumor immunology and medical oncology[1].This special issue of Cellular&Molecular Immunology(CMI)compiles a series of review articles,presenting state-ofthe-art literature and concepts focused on several important aspects concerning the most recent advancement in immune sensitive and resistant mechanisms in the tumor microenvironment,and their relevance in cancer therapy.展开更多
Bone marrow is thought to be a primary hematopoietic organ. However, accumulated evidences demonstrate that active function and trafficking of immune cells, including regulatory T cells, conventional T cells, B cells,...Bone marrow is thought to be a primary hematopoietic organ. However, accumulated evidences demonstrate that active function and trafficking of immune cells, including regulatory T cells, conventional T cells, B cells, dendritic cells, natural killer T (NKT) cells, neutrophils, myeloid-derived suppressor cells and mesenchymal stem cells, are observed in the bone marrow. Furthermore, bone marrow is a predetermined metastatic location for multiple human tumors. In this review, we discuss the immune network in the bone marrow. We suggest that bone marrow is an immune regulatory organ capable of fine tuning immunity and may be a potential therapeutic target for immunotherapy and immune vaccination.展开更多
文摘Pyroptosis,an inflammatory form of programmed cell death,eliminates a niche where pathogens replicate,providing overall benefits to a host.When left uncontrolled,pyroptosis can lead to severe pathology.Overactive pyroptotic activation has been implicated in neuroinflammation,cardiovascular disease,acute respiratory distress syndrome(ARDS),and many other diseases[1,2,3].Because of its multiple and permanent consequences,pyroptosis is a highly regulated signaling pathway.Major regulators of pyroptosis are NLR inflammasomes,which are activated by various“danger”signals such as ATP.
文摘Chronic inflammatory responses have long been observed to be associated with various types of cancer and play decisive roles at different stages of cancer development. Inflammasomes, which are potent induc- ers of interleukin （IL）-I~ and IL-18 during infammation, are large protein complexes typically consisting of a Nod-like receptor （NLR）, the adapter protein ASC, and Caspase-1. During malignant transformation or cancer therapy, the inflammasomes are postulated to become activated in response to danger signals arising from the tumors or from therapy-induced damage to the tumor or healthy tissue. The activation of inflammasomes plays diverse and sometimes contrasting roles in cancer promotion and therapy depending on the specific con- text. Here we summarize the role of different inflamma- some complexes in cancer progression and therapy. Inflammasome components and pathways may provide novel targets to treat certain types of cancer; however, using such agents should be cautiously evaluated due to the complex roles that inflammasomes and pro- inflammatory cytokines play in immunity.
基金This work was supported by the Babcock Endowment Fund(L.C.T.and J.E.G.),the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under award numbers R01-AR060802(J.E.G.),P30-AR075043(J.E.G.),and K01-AR072129(L.C.T.),and the National Institute of Allergy and Infectious Diseases under award number R01-AR069071(J.E.G.),the A.Alfred Taubman Medical Research Institute(J.E.G.and J.M.K.),the National Psoriasis Foundation(J.E.G,N.L.W.,J.M.K.,E.M.,and L.C.T.),and the Parfait Emerging Scholar Award(J.M.K.).L.C.T.is supported by the Dermatology Foundation,the Arthritis National Research Foundation,and the National Psoriasis Foundation.
文摘Psoriasis is a chronic inflammatory skin condition that has a fairly wide range of clinical presentations.Plaque psoriasis,which is the most common manifestation of psoriasis,is located on one end of the spectrum,dominated by adaptive immune responses,whereas the rarer pustular psoriasis lies on the opposite end,dominated by innate and autoinflammatory immune responses.In recent years,genetic studies have identified six genetic variants that predispose to pustular psoriasis,and these have highlighted the role of IL-36 cytokines as central to pustular psoriasis pathogenesis.In this review,we discuss the presentation and clinical subtypes of pustular psoriasis,contribution of genetic predisposing variants,critical role of the IL-36 family of cytokines in disease pathophysiology,and treatment perspectives for pustular psoriasis.We further outline the application of appropriate mouse models for the study of pustular psoriasis and address the outstanding questions and issues related to our understanding of the mechanisms involved in pustular psoriasis.
文摘While immunotherapy has had an important impact on cancer treatment,only approximately a quarter of patients respond to these treatments.Why does it work in some patients but not in other patients?How can we improve the therapeutic efficacy of current immunotherapy?Are there potential new strategies to tackle this problem?The answers to these questions may rely on our in-depth understanding of the basic mechanisms of the cancer immune response,immunotherapeutic efficacy,and resistance.
基金We thank Tasuko Honjo for providing Rbpj^flox/flox mice, Keiko Ozato for providing Ifr8^-/- mice, and Karmen Au for technical assistance. LBI and BZ are supported by the grants from NIH. XH is supported by the National Basic Research Program （973 Program） （No. 2015CB943201）, National Natural Science Foundation of China Young Investigator Award 81422019, and funds from Peking-Tsin- ghua Center of Life Sciences.
文摘Development of alternatively activated （M2） macrophage phenotypes is a complex process that is coordinately regulated by a plethora of pathways and factors. Here, we report that RBP-J, a DNA-binding protein that integrates signals from multiple pathways including the Notch pathway, is critically involved in polarization of M2 macrophages. Mice deficient in RBP-J in the myeloid compartment exhibited impaired M2 phenotypes in vivo in a chitin-induced model of M2 polarization. Consistent with the in vivo findings, M2 polarization was partially compromised in vitro in Rbpj-deficient macrophages as demonstrated by reduced expression of a subset of M2 effector molecules including arginase 1. Functionally, myeloid Rbpj deficiency impaired M2 effector functions including recruitment of eosinophils and suppression of T cell proliferation. Collectively, we have identified RBP- Jas an essential regulator of differentiation and function of alternatively activated macrophages.
基金This work was supported in part by U.S.NIH/NCI R01 grants(CA217648,CA123088,CA099985,CA193136,CA152470)the NIH through the University of Michigan Rogel Cancer Center Grant(CA46592).
文摘The majority of colorectal cancer patients are not responsive to immune checkpoint blockade(ICB).The interferon gamma(IFNγ)signaling pathway drives spontaneous and ICB-induced antitumor immunity.In this review,we summarize recent advances in the epigenetic,genetic,and functional integrity of the IFNγsignaling pathway in the colorectal cancer microenvironment and its immunological relevance in the therapeutic efficacy of and resistance to ICB.Moreover,we discuss how to target IFNγsignaling to inform novel clinical trials to treat patients with colorectal cancer.
基金This work was supported in part by research grants from the NIH/NCI for WZ(CA248430,CA214911,CA123088,CA099985,CA193136,and CA152470)the NIH through the University of Michigan Rogel Cancer Center Support Grant(P30CA46592).
文摘Cancer immunotherapy,including immune checkpoint blockade and CAR-T cell therapy,has introduced revolutionary approaches to treating patients with cancer.The success and hope of cancer immunotherapy have continuously stimulated high interest in dissecting immunotherapy resistance mechanisms,researching previously unknown therapeutic targets,and informing novel clinical trials in cancer therapy.The notion that the tumor microenvironment holds the key to understanding tumor immunity and developing novel immunotherapy has been well established in the field of tumor immunology and medical oncology[1].This special issue of Cellular&Molecular Immunology(CMI)compiles a series of review articles,presenting state-ofthe-art literature and concepts focused on several important aspects concerning the most recent advancement in immune sensitive and resistant mechanisms in the tumor microenvironment,and their relevance in cancer therapy.
基金NIH/NCI R01 grants(R01CA133620)(WZ)and the NIH through the University of Michigan’s Cancer Center Support Grant(5 P30 CA46592).
文摘Bone marrow is thought to be a primary hematopoietic organ. However, accumulated evidences demonstrate that active function and trafficking of immune cells, including regulatory T cells, conventional T cells, B cells, dendritic cells, natural killer T (NKT) cells, neutrophils, myeloid-derived suppressor cells and mesenchymal stem cells, are observed in the bone marrow. Furthermore, bone marrow is a predetermined metastatic location for multiple human tumors. In this review, we discuss the immune network in the bone marrow. We suggest that bone marrow is an immune regulatory organ capable of fine tuning immunity and may be a potential therapeutic target for immunotherapy and immune vaccination.
