Pancreatic cancer（PCA） is one of the most aggressive tumors with few effective treatment modalities. It is the 4th and 7th leading cause of cancer death in the United States and China, respectively. At the time of d...Pancreatic cancer（PCA） is one of the most aggressive tumors with few effective treatment modalities. It is the 4th and 7th leading cause of cancer death in the United States and China, respectively. At the time of diagnosis, only 20% of cases present with a resectable tumor, and about 40% with a locally advanced tumor that is considered unresectable. Even resected patients still have a poor prognosis, with an incidence of local recurrence ranging from 20% to 60%. It is also reported that up to 30% of PCA patients die from locally obstructive disease with few or no distant metastases. These findings have highlighted the importance of local radiation therapy in the treatment of PCA. As the role of conventional chemoradiotherapy remains controversial, the dawn of the pancreas stereotactic body radiation therapy（SBRT） era represents a potential paradigm shift in the management of PCA. SBRT delivers a higher biological effective dose to the tumor with sharp dose escalation in a shorter treatment time course. Pancreas SBRT is a novel therapeutic option to achieve local tumor control with minimal toxicity. Herein, we review the advancement of SBRT for PCA patients with different stages of pancreatic adenocarcinoma.展开更多
Hepatocellular carcinoma(HCC),one of the most common liver cancers,often has a poor prognosis when it involves macrovascular invasion.Oncological emergencies including pulmonary embolism,heart failure,and even sudden ...Hepatocellular carcinoma(HCC),one of the most common liver cancers,often has a poor prognosis when it involves macrovascular invasion.Oncological emergencies including pulmonary embolism,heart failure,and even sudden death could happen when it develops a tumor thrombus(TT)in the inferior vena cava(IVC)or right atrium(RA),indicating an exceptionally grim prognosis(1).Although systemic therapy is the only standard treatment recommended by guidelines(2),other treatment modalities are explored including surgery,radiotherapy,etc.in some centers.Surgery,as the only potential curative treatment,has been explored in several selected cases.A case of long-term survival of 15 years and cancer-free survival of 9 years was reported by surgical resection with a heart-first approach under cardiopulmonary bypass(CPB)(3),suggesting that aggressive surgery together with multidisciplinary treatments might achieve long survival.However,due to the aggressiveness and challenge of surgical resection-massive resection area,potential significant blood loss,and bypass needed,surgical resection is applied in very limited centers.Nevertheless,safety,efficacy,and long-term survival benefits for these patients are poorly investigated.展开更多
As one of the four major means of cancer treatment including surgery,radiotherapy(RT),chemotherapy,immunotherapy,RT can be applied to various cancers as both a radical cancer treatment and an adjuvant treatment before...As one of the four major means of cancer treatment including surgery,radiotherapy(RT),chemotherapy,immunotherapy,RT can be applied to various cancers as both a radical cancer treatment and an adjuvant treatment before or after surgery.Although RT is an important modality for cancer treatment,the consequential changes caused by RT in the tumor microenvironment(TME)have not yet been fully elucidated.RT-induced damage to cancer cells leads to different outcomes,such as survival,senescence,or death.During RT,alterations in signaling pathways result in changes in the local immune microenvironment.However,some immune cells are immunosuppressive or transform into immunosuppressive phenotypes under specific conditions,leading to the development of radioresistance.Patients who are radioresistant respond poorly to RT and may experience cancer progression.Given that the emergence of radioresistance is inevitable,new radiosensitization treatments are urgently needed.In this review,we discuss the changes in irradiated cancer cells and immune cells in the TME under different RT regimens and describe existing and potential molecules that could be targeted to improve the therapeutic effects of RT.Overall,this review highlights the possibilities of synergistic therapy by building on existing research.展开更多
Macrophages have a leading position in the tumor microenvironment(TME)which paves the way to carcinogenesis.Initially,monocytes and macrophages are recruited to the sites where the tumor develops.Under the guidance of...Macrophages have a leading position in the tumor microenvironment(TME)which paves the way to carcinogenesis.Initially,monocytes and macrophages are recruited to the sites where the tumor develops.Under the guidance of different microenvironmental signals,macrophages would polarize into two functional phenotypes,named as classically activated macrophages(M1)and alternatively activated macrophages(M2).Contrary to the anti-tumor effect of M1,M2 exerts anti-inflammatory and tumorigenic characters.In progressive tumor,M2 tumor-associated macrophages(TAMs)are in the majority,being vital regulators reacting upon TME.This review elaborates on the role of TAMs in tumor progression.Furthermore,prospective macrophage-focused therapeutic strategies,including drugs not only in clinical trials but also at primary research stages,are summarized followed by a discussion about their clinical application values.Nanoparticulate systems with efficient drug delivery and improved antitumor effect are also summed up in this article.展开更多
γδT cells are a conserved population of innate lymphocytes with diverse structural and functional heterogeneity that participate in various immune responses during tumor progression. γδT cells perform potent immun...γδT cells are a conserved population of innate lymphocytes with diverse structural and functional heterogeneity that participate in various immune responses during tumor progression. γδT cells perform potent immunosurveillance by exerting direct cytotoxicity, strong cytokine production and indirect antitumor immune responses. However, certain γδT-cell subsets also contribute to tumor progression by facilitating cancer-related inflammation and immunosuppression. Here, we review recent observations regarding the antitumor and protumor roles of major structural and functional subsets of human γδT cells, describing how these subsets are activated and polarized, and how these events relate to subsequent function in tumor immunity. These studies provide insights into the manipulation of γδT-cell function to facilitate more targeted approaches for tumor therapy.展开更多
Bone is a common organ affected by metastasis in various advanced cancers,including lung,breast,prostate,colorectal,and melanoma.Once a patient is diagnosed with bone metastasis,the patient’s quality of life and over...Bone is a common organ affected by metastasis in various advanced cancers,including lung,breast,prostate,colorectal,and melanoma.Once a patient is diagnosed with bone metastasis,the patient’s quality of life and overall survival are significantly reduced owing to a wide range ofmorbidities and the increasing difficulty of treatment.Many studies have shown that bone metastasis is closely related to bone microenvironment,especially bone immune microenvironment.However,the effects of various immune cells in the bone microenvironment on bone metastasis remain unclear.Here,we described the changes in various immune cells during bone metastasis and discussed their related mechanisms.Osteoblasts,adipocytes,and other non-immune cells closely related to bone metastasis were also included.This review also summarized the existing treatment methods and potential therapeutic targets,and provided insights for future studies of cancer bone metastasis.展开更多
基金the National Natural Science Foundation of China (No. 81071823)Innovative Multidisciplinary Team for Diagnosis and Treatment of Pancreatic Cancer of Zhejiang Province, China (No. 2013TD06)
文摘Pancreatic cancer（PCA） is one of the most aggressive tumors with few effective treatment modalities. It is the 4th and 7th leading cause of cancer death in the United States and China, respectively. At the time of diagnosis, only 20% of cases present with a resectable tumor, and about 40% with a locally advanced tumor that is considered unresectable. Even resected patients still have a poor prognosis, with an incidence of local recurrence ranging from 20% to 60%. It is also reported that up to 30% of PCA patients die from locally obstructive disease with few or no distant metastases. These findings have highlighted the importance of local radiation therapy in the treatment of PCA. As the role of conventional chemoradiotherapy remains controversial, the dawn of the pancreas stereotactic body radiation therapy（SBRT） era represents a potential paradigm shift in the management of PCA. SBRT delivers a higher biological effective dose to the tumor with sharp dose escalation in a shorter treatment time course. Pancreas SBRT is a novel therapeutic option to achieve local tumor control with minimal toxicity. Herein, we review the advancement of SBRT for PCA patients with different stages of pancreatic adenocarcinoma.
基金supported by grants from the National Natural Science Foundation of China(No.82203078,J.Y.,No.82073332,Q.W.)Natural Science Foundation of Zhejiang Province(No.LQ22H160030,J.Y.).
文摘Hepatocellular carcinoma(HCC),one of the most common liver cancers,often has a poor prognosis when it involves macrovascular invasion.Oncological emergencies including pulmonary embolism,heart failure,and even sudden death could happen when it develops a tumor thrombus(TT)in the inferior vena cava(IVC)or right atrium(RA),indicating an exceptionally grim prognosis(1).Although systemic therapy is the only standard treatment recommended by guidelines(2),other treatment modalities are explored including surgery,radiotherapy,etc.in some centers.Surgery,as the only potential curative treatment,has been explored in several selected cases.A case of long-term survival of 15 years and cancer-free survival of 9 years was reported by surgical resection with a heart-first approach under cardiopulmonary bypass(CPB)(3),suggesting that aggressive surgery together with multidisciplinary treatments might achieve long survival.However,due to the aggressiveness and challenge of surgical resection-massive resection area,potential significant blood loss,and bypass needed,surgical resection is applied in very limited centers.Nevertheless,safety,efficacy,and long-term survival benefits for these patients are poorly investigated.
基金supported by the grant from the National Natural Science Foundation of China(82173089,T.Z.,82073332,Q.W,81930079,J.H.,U22A2031,J.H,82073142,D.W.,82073151,C.N.,82273275,C.N.)National Key Research and Development Program(2022YFA1105200,J.H.)+3 种基金Natural Science Foundation of Zhejiang Province(LY21H100004,T.Z:,LY19H160050,D.W.,LR19H160001,C.N.,LGF22H060010,Z.X.)Zhejiang Research and Development Project(2022C03019,J.H.)Medical Science and Technology Project of Zhejiang Province(2021KY697,Z.X.,2021RC063,T.Z.)Beijing CSCO Clinical Oncology Research Foundation(Y-2020Sciclone/ms-0099,T.Z.,Y-2019Sciclone-019,T.Z.).
文摘As one of the four major means of cancer treatment including surgery,radiotherapy(RT),chemotherapy,immunotherapy,RT can be applied to various cancers as both a radical cancer treatment and an adjuvant treatment before or after surgery.Although RT is an important modality for cancer treatment,the consequential changes caused by RT in the tumor microenvironment(TME)have not yet been fully elucidated.RT-induced damage to cancer cells leads to different outcomes,such as survival,senescence,or death.During RT,alterations in signaling pathways result in changes in the local immune microenvironment.However,some immune cells are immunosuppressive or transform into immunosuppressive phenotypes under specific conditions,leading to the development of radioresistance.Patients who are radioresistant respond poorly to RT and may experience cancer progression.Given that the emergence of radioresistance is inevitable,new radiosensitization treatments are urgently needed.In this review,we discuss the changes in irradiated cancer cells and immune cells in the TME under different RT regimens and describe existing and potential molecules that could be targeted to improve the therapeutic effects of RT.Overall,this review highlights the possibilities of synergistic therapy by building on existing research.
基金supported by the National Natural Science Foundation of China(Nos.81673022,81572952 and 81373346)National Key R&D Program of China(No.2017YFE0102200)
文摘Macrophages have a leading position in the tumor microenvironment(TME)which paves the way to carcinogenesis.Initially,monocytes and macrophages are recruited to the sites where the tumor develops.Under the guidance of different microenvironmental signals,macrophages would polarize into two functional phenotypes,named as classically activated macrophages(M1)and alternatively activated macrophages(M2).Contrary to the anti-tumor effect of M1,M2 exerts anti-inflammatory and tumorigenic characters.In progressive tumor,M2 tumor-associated macrophages(TAMs)are in the majority,being vital regulators reacting upon TME.This review elaborates on the role of TAMs in tumor progression.Furthermore,prospective macrophage-focused therapeutic strategies,including drugs not only in clinical trials but also at primary research stages,are summarized followed by a discussion about their clinical application values.Nanoparticulate systems with efficient drug delivery and improved antitumor effect are also summed up in this article.
文摘γδT cells are a conserved population of innate lymphocytes with diverse structural and functional heterogeneity that participate in various immune responses during tumor progression. γδT cells perform potent immunosurveillance by exerting direct cytotoxicity, strong cytokine production and indirect antitumor immune responses. However, certain γδT-cell subsets also contribute to tumor progression by facilitating cancer-related inflammation and immunosuppression. Here, we review recent observations regarding the antitumor and protumor roles of major structural and functional subsets of human γδT cells, describing how these subsets are activated and polarized, and how these events relate to subsequent function in tumor immunity. These studies provide insights into the manipulation of γδT-cell function to facilitate more targeted approaches for tumor therapy.
基金National Natural Science Foundation of China,Grant/Award Numbers:82173089,82073332,82073142Natural Science Foundation of Zhejiang Province,Grant/Award Numbers:LY21H100004,LY19H160050+1 种基金Medical Science and Technology Project of Zhejiang Province,Grant/Award Number:2021RC063Chinese Society of Clinical Oncology,Grant/Award Numbers:Y-2020Sciclone/ms-0099,Y-2019Sciclone-019。
文摘Bone is a common organ affected by metastasis in various advanced cancers,including lung,breast,prostate,colorectal,and melanoma.Once a patient is diagnosed with bone metastasis,the patient’s quality of life and overall survival are significantly reduced owing to a wide range ofmorbidities and the increasing difficulty of treatment.Many studies have shown that bone metastasis is closely related to bone microenvironment,especially bone immune microenvironment.However,the effects of various immune cells in the bone microenvironment on bone metastasis remain unclear.Here,we described the changes in various immune cells during bone metastasis and discussed their related mechanisms.Osteoblasts,adipocytes,and other non-immune cells closely related to bone metastasis were also included.This review also summarized the existing treatment methods and potential therapeutic targets,and provided insights for future studies of cancer bone metastasis.
