The 8^th International Workshop on Human Leucocyte Differentiation Antigens (chaired by HZ and managed by BS) was run over a 4-year period and culminated in a conference in December 2004. Here we review the achievem...The 8^th International Workshop on Human Leucocyte Differentiation Antigens (chaired by HZ and managed by BS) was run over a 4-year period and culminated in a conference in December 2004. Here we review the achievements of the HLDA Workshops and provide links to information on CD molecules and antibodies against them, including the 93 new CDs assigned in the 8^th Workshop. We consider what remains to be achieved (including an estimate of the number of leucocyte surface molecules still to be discovered), and how the field can best move forward.展开更多
Background The mechanism of chronic immune activation and impairment of HIV-specific immune responses during chronic infection is not fully understood. However, it is known that high immune activation leads to more ra...Background The mechanism of chronic immune activation and impairment of HIV-specific immune responses during chronic infection is not fully understood. However, it is known that high immune activation leads to more rapid progression to AIDS. We hypothesize that CD4^+ T cell-mediated viral antigen presentation contributes to this pathologic immune activation in HIV-infected individuals. Methods HIV-specific T cells, responding to noninfectious HIV-1 virions as antigen, were measured by flow cytometric assays. These experimental conditions reflect the in vivo condition where noninfectious HIV-1 represents more than 99% of the antigens. Results CD4^+ T cells purified from HIV-infected individuals were capable of cross presenting exogenous noninfectious HIV-1 virions to HIV-1-specific CD8^+ T cells. Cross presentation required the entry of HIV-1 to CD4^+ T cells and antigen translocation from endoplasmic reticulum to the Golgi complex. Blocking CD4^+ mediated activation of HIV-specific CD8^+ T cells and redirecting the viral antigens to antigen presenting cells improved HIV-specific T cell responses. Contusions One possible cause of chronic immune activation and impairment of HIV-1 specific T cell responses is represented by HIV-1 harboring CD4^+ T cells cross presenting HIV-1 antigen to activate CD8^+ T cells. This new mechanism provides the first evidence that cross presentation of noninfectious HIV-1 virions play a role in the immunopathogenesis of HIV-1 infection.展开更多
Objective:To investigate the prevalence of microbial antigenic components of circulating immune complexes amongst grades of CD4 T lymphocyte counts in HIV sero positive and seronegative participants.Methods:Polyethele...Objective:To investigate the prevalence of microbial antigenic components of circulating immune complexes amongst grades of CD4 T lymphocyte counts in HIV sero positive and seronegative participants.Methods:Polyethelene glycol(PEG-600) and buffering methods of precipitation and dissociation of immune complexes was used to generate immune solution from sera of 100 HIV sero-positive and 100 HIV sero-negative participants.These were categorized into 3 grades based on CD4 count:】 500 cell/mm,200-499 cell/mm3 and 【200 cell/mm3.The immune solutions were assayed using membrane based immunoassay and antibody titration, along side its unprocessed serum for detection of various microbial antigens and or antibodies. CD4 T cell counts were estimated using Patec Cyflow SL-3 Germany.Results:Antigenic component of immune complexes of various infectious agents was detected in 99 and 70 HIV seropositive and HIV sero-negative participants,respectively.In group A,there were 10 HIV positive participants,including 4(40.0%) had circulating immune complexes(CICs) due to Salmonella species only:1(10.0%) due to Salmonella-Plasmodium falciparum(P.falciparum),SalmonellaP. falciparum-HCV and P.falciparum antigens,respectively.In group B,45(45.4%) HIV seropositive participants with CICs had CD4 T lymphocyte count between 200-499 cells/mm^3.Out of these,20(44.4%) had CICs due to Salmonella species only:9(20%) due to Salmonella-P. falciparum.In group C,there were 44(44.4%) HIV sero-positive participants,including 3(6.8%) due to Salmonella species only:24(54.4%) due to Salmonella-P.falciparum:2(4.5%) due to P. falciparum only.Conclusions:In HIV sero-positive participants,presence of heterogeneity of Salmonella species-P.falciparum antigens was highly incriminated in CD4 count depletion but not homogeneity of malaria parasites antigens.Malaria parasites antigens only were incriminated in CD4^+ count depletion amongst HIV sero-negative participants.Before taking any decision on the management of HIV-1-positive individuals,their malaria and Salmonella paratyphi status should be assessed,but not malaria status alone.展开更多
T cells engineered to express chimeric antigen receptors (CARs) combining an external antibody binding domain with the CD3ζ T cell receptor (TCR) signaling domain for triggering cell activation are being used for imm...T cells engineered to express chimeric antigen receptors (CARs) combining an external antibody binding domain with the CD3ζ T cell receptor (TCR) signaling domain for triggering cell activation are being used for immunotherapeutic targeting of tumor cells in a non-HLA restricted manner. In this study we transduced T cells with a CD19-CAR construct containing a truncated CD34 gene (tCD34) marker and used these to target the B cell antigen CD19 on the surface of a Hodgkin’s lymphoma (HL) cell line (L591) both in vitro and in vivo. Levels of tCD34 expression in transduced peripheral blood mononuclear cells (PBMCs) ranged from 6% - 20% and this was increased to 82% after selection for transduced tCD34+ cells. In vitro cytotoxicity testing on a CD19+ HL cell line (L591) showed specific cell lysis initiated by the CD19-CAR transduced PBMCs. Importantly, CD19-CAR T cells prevented the growth of L591 HL tumor cells when co-injected subcutaneously (sc) in 6/6 severe combined immunodeficient (SCID) mice. There was no evidence of anti-tumor activity when CD19-CAR T cells were infused intravenously (iv) at the same time as L591 HL tumor cells were injected sc. However, 3/6 SCID mice showed tumor rejection within 83 days after iv infusion of CD19-CAR T cells 3 - 9 days after establishment of L591 HL tumors, while all control animals succumbed to tumors within 60 days. Interestingly, immuno-histochemical analysis of L591 HL tumors demonstrated that CD19-CAR T cells were detected not earlier than 11 days after infusion within the tumor mass. These results suggest that CD19 is a potentially attractive target for the immunotherapy of HL.展开更多
AIM: To investigate the role of regulatory T (Treg) cells in CD4^+ T cell-mediated bladder autoimmune infammation. METHODS: Urothelium-ovalbumin (URO-OVA)/OT-II mice, a double transgenic line that expresses the...AIM: To investigate the role of regulatory T (Treg) cells in CD4^+ T cell-mediated bladder autoimmune infammation. METHODS: Urothelium-ovalbumin (URO-OVA)/OT-II mice, a double transgenic line that expresses the membrane form of the model antigen (Ag) OVA as a self-Ag on the urothelium and the OVA-specific CD4^+ T cell receptor specifc for the I-Ab/OVA323-339 epitope in the periphery, were developed to provide an autoimmune environment for investigation of the role of Treg cells in bladder autoimmune infammation. To facilitate Treg cell analysis, we further developed URO-OVA^GFP-Foxp3/OT-II mice, a derived line of URO-OVA/OT-II mice that express the green fuorescent protein (GFP)-forkhead box protein P3 (Foxp3) fusion protein. RESULTS: URO-OVA/OT-II mice failed to develop bladder infammation despite the presence of autoreactive CD4^+ T cells. By monitoring GFP-positive cells, bladder infltration of CD4^+ Treg cells was observed in URO-OVA^GFP-Foxp3/OT-II mice. The infiltrating Treg cells were functionally active and expressed Treg cell effector molecule as well as marker mRNAs including transforming growth factor-β, interleukin (IL)-10, fibrinogen-like protein 2, and glucocorticoid-induced tumor necrosis factor receptor (GITR). Studies further revealed that Treg cells from URO-OVA^GFP-Foxp3/OT-II mice were suppressive and inhibited autoreactive CD4^+ T cell proliferation and interferon (IFN)-g production in response to OVA Ag stimulation. Depletion of GITR-positive cells led to spontaneous development of bladder infammation and expression of inflammatory factor mRNAs for IFN-γ, IL-6, tumor necrosis factor-α and nerve growth factor in URO-OVA^GFP-Foxp3/OT-II mice. CONCLUSION: Treg cells specifc for bladder epithelial Ag play an important role in immunological homeostasis and the control of CD4^+ T cell-mediated bladder autoimmune infammation.展开更多
Background:Chimeric antigen receptor T(CAR-T)cell therapy has achieved marked therapeutic success in ameliorating hematological malignancies.However,there is an extant void in the clinical guidelines concerning the mo...Background:Chimeric antigen receptor T(CAR-T)cell therapy has achieved marked therapeutic success in ameliorating hematological malignancies.However,there is an extant void in the clinical guidelines concerning the most effective chemotherapy regimen prior to chimeric antigen receptor T(CAR-T)cell therapy,as well as the optimal timing for CAR-T cell infusion post-chemotherapy.Materials and Methods:We employed cell-derived tumor xenograft(CDX)murine models to delineate the optimal pre-conditioning chemotherapy regimen and timing for CAR-T cell treatment.Furthermore,transcriptome sequencing was implemented to identify the therapeutic targets and elucidate the underlying mechanisms governing the treatment regimen.Results:Our preclinical in vivo evaluation determined that a combination of cyclophosphamide and fludarabine,followed by the infusion of CD19 CAR-T cells five days subsequent to the chemotherapy,exerts the most efficacious therapeutic effect in B-cell hematological malignancies.Concurrently,RNA-seq data indicated that the therapeutic efficacy predominantly perturbs tumor cell metabolism,primarily through the inhibition of key mitochondrial targets,such as C-Jun Kinase enzyme(C-JUN).Conclusion:In summary,the present study offers critical clinical guidance and serves as an authoritative reference for the deployment of CD19 CAR-T cell therapy in the treatment of B-cell hematological malignancies.展开更多
Dysregulation of lipid metabolism is a key characteristic of the tumor microenvironment,where tumor cells utilize lipids for proliferation,survival,metastasis,and evasion of immune surveillance.Lipid metabolism has be...Dysregulation of lipid metabolism is a key characteristic of the tumor microenvironment,where tumor cells utilize lipids for proliferation,survival,metastasis,and evasion of immune surveillance.Lipid metabolism has become a critical regulator of CD8+T-cell-mediated antitumor immunity,with excess lipids in the tumor microenvironment impeding CD8+T-cell activities.Considering the limited efficacy of immunotherapy in many solid tumors,targeting lipid metabolism to enhance CD8+T-cell effector functions could significantly improve immunotherapy outcomes.In this review,we examine recent findings on how lipid metabolic processes,including lipid uptake,synthesis,and oxidation,regulate CD8+T cells within tumors.We also assessed the impact of different lipids on CD8+T-cell-mediated antitumor immunity,with a particular focus on how lipid metabolism affects mitochondrial function in tumor-infiltrating CD8+T cells.Furthermore,as cancer is a systemic disease,we examined systemic factors linking lipid metabolism to CD8+T-cell effector function.Finally,we summarize current therapeutic approaches that target lipid metabolism to increase antitumor immunity and enhance immunotherapy.Understanding the molecular and functional interplay between lipid metabolism and CD8+T cells offers promising therapeutic opportunities for cancer treatment.展开更多
目的 探讨CD15抗原和组织蛋白酶D(Cath-D)在食管癌的表达意义及其相互关系。 方法 应用微波-LSAB免疫组化法,观察65例食管癌组织(男46例,女19例;平均年龄54岁;均为鳞癌)中CD15和Cath-D的表达阳性率及其相互关系。 结果 食管癌CD15和CD...目的 探讨CD15抗原和组织蛋白酶D(Cath-D)在食管癌的表达意义及其相互关系。 方法 应用微波-LSAB免疫组化法,观察65例食管癌组织(男46例,女19例;平均年龄54岁;均为鳞癌)中CD15和Cath-D的表达阳性率及其相互关系。 结果 食管癌CD15和CD阳性率分别为58%(38/65例)和65%(42/65例);食管癌CD15和Cath-D表达与性别、年龄、肿瘤部位、大体类型及肿瘤大小无关(P>0.05)。CD15和Cath-D表达阳性率:鳞癌Ⅲ级(88%,14/16 vs 100%,16/16)均显著高于鳞癌Ⅰ级(43%,6/14 vs 50%,7/14)和鳞癌Ⅱ级(51%,18/35 vs 54%,19/35,P<0.05);外膜层浸润(74%,20/27 vs82%,22/27)显著高于肌层浸润(47%,18/38 vs 53%,20/38,P<0.05);有淋巴结转移组(72%,26/36 vs 78%,28/38)显著高于无淋巴结转移组(41%,12/29 vs 48%、14/29,P<0.025);死亡组(70%,31/44 vs 77%,34/44)显著高于五年生存组(33%,7/21 vs 38%,8/21,P<0.01)。CD15阳性的肿瘤Cath-D阳性率显著高于CD15阴性者(82%,31/38 vs41%,11/27),CD15表达与Cath-D表达呈正相关(r=0.42,P<0.01)。 结论 检测CD15和Cath-D表达对判断食管癌恶性程度、预测其侵袭转移趋势和预后及指导治疗有重要意义。食管癌CD15与Cath-D表达具有相互协同作用可能。展开更多
文摘The 8^th International Workshop on Human Leucocyte Differentiation Antigens (chaired by HZ and managed by BS) was run over a 4-year period and culminated in a conference in December 2004. Here we review the achievements of the HLDA Workshops and provide links to information on CD molecules and antibodies against them, including the 93 new CDs assigned in the 8^th Workshop. We consider what remains to be achieved (including an estimate of the number of leucocyte surface molecules still to be discovered), and how the field can best move forward.
基金This study was supported by a grant from the Major Basic Project of China (973) (No. 2005CB522903).
文摘Background The mechanism of chronic immune activation and impairment of HIV-specific immune responses during chronic infection is not fully understood. However, it is known that high immune activation leads to more rapid progression to AIDS. We hypothesize that CD4^+ T cell-mediated viral antigen presentation contributes to this pathologic immune activation in HIV-infected individuals. Methods HIV-specific T cells, responding to noninfectious HIV-1 virions as antigen, were measured by flow cytometric assays. These experimental conditions reflect the in vivo condition where noninfectious HIV-1 represents more than 99% of the antigens. Results CD4^+ T cells purified from HIV-infected individuals were capable of cross presenting exogenous noninfectious HIV-1 virions to HIV-1-specific CD8^+ T cells. Cross presentation required the entry of HIV-1 to CD4^+ T cells and antigen translocation from endoplasmic reticulum to the Golgi complex. Blocking CD4^+ mediated activation of HIV-specific CD8^+ T cells and redirecting the viral antigens to antigen presenting cells improved HIV-specific T cell responses. Contusions One possible cause of chronic immune activation and impairment of HIV-1 specific T cell responses is represented by HIV-1 harboring CD4^+ T cells cross presenting HIV-1 antigen to activate CD8^+ T cells. This new mechanism provides the first evidence that cross presentation of noninfectious HIV-1 virions play a role in the immunopathogenesis of HIV-1 infection.
文摘Objective:To investigate the prevalence of microbial antigenic components of circulating immune complexes amongst grades of CD4 T lymphocyte counts in HIV sero positive and seronegative participants.Methods:Polyethelene glycol(PEG-600) and buffering methods of precipitation and dissociation of immune complexes was used to generate immune solution from sera of 100 HIV sero-positive and 100 HIV sero-negative participants.These were categorized into 3 grades based on CD4 count:】 500 cell/mm,200-499 cell/mm3 and 【200 cell/mm3.The immune solutions were assayed using membrane based immunoassay and antibody titration, along side its unprocessed serum for detection of various microbial antigens and or antibodies. CD4 T cell counts were estimated using Patec Cyflow SL-3 Germany.Results:Antigenic component of immune complexes of various infectious agents was detected in 99 and 70 HIV seropositive and HIV sero-negative participants,respectively.In group A,there were 10 HIV positive participants,including 4(40.0%) had circulating immune complexes(CICs) due to Salmonella species only:1(10.0%) due to Salmonella-Plasmodium falciparum(P.falciparum),SalmonellaP. falciparum-HCV and P.falciparum antigens,respectively.In group B,45(45.4%) HIV seropositive participants with CICs had CD4 T lymphocyte count between 200-499 cells/mm^3.Out of these,20(44.4%) had CICs due to Salmonella species only:9(20%) due to Salmonella-P. falciparum.In group C,there were 44(44.4%) HIV sero-positive participants,including 3(6.8%) due to Salmonella species only:24(54.4%) due to Salmonella-P.falciparum:2(4.5%) due to P. falciparum only.Conclusions:In HIV sero-positive participants,presence of heterogeneity of Salmonella species-P.falciparum antigens was highly incriminated in CD4 count depletion but not homogeneity of malaria parasites antigens.Malaria parasites antigens only were incriminated in CD4^+ count depletion amongst HIV sero-negative participants.Before taking any decision on the management of HIV-1-positive individuals,their malaria and Salmonella paratyphi status should be assessed,but not malaria status alone.
文摘T cells engineered to express chimeric antigen receptors (CARs) combining an external antibody binding domain with the CD3ζ T cell receptor (TCR) signaling domain for triggering cell activation are being used for immunotherapeutic targeting of tumor cells in a non-HLA restricted manner. In this study we transduced T cells with a CD19-CAR construct containing a truncated CD34 gene (tCD34) marker and used these to target the B cell antigen CD19 on the surface of a Hodgkin’s lymphoma (HL) cell line (L591) both in vitro and in vivo. Levels of tCD34 expression in transduced peripheral blood mononuclear cells (PBMCs) ranged from 6% - 20% and this was increased to 82% after selection for transduced tCD34+ cells. In vitro cytotoxicity testing on a CD19+ HL cell line (L591) showed specific cell lysis initiated by the CD19-CAR transduced PBMCs. Importantly, CD19-CAR T cells prevented the growth of L591 HL tumor cells when co-injected subcutaneously (sc) in 6/6 severe combined immunodeficient (SCID) mice. There was no evidence of anti-tumor activity when CD19-CAR T cells were infused intravenously (iv) at the same time as L591 HL tumor cells were injected sc. However, 3/6 SCID mice showed tumor rejection within 83 days after iv infusion of CD19-CAR T cells 3 - 9 days after establishment of L591 HL tumors, while all control animals succumbed to tumors within 60 days. Interestingly, immuno-histochemical analysis of L591 HL tumors demonstrated that CD19-CAR T cells were detected not earlier than 11 days after infusion within the tumor mass. These results suggest that CD19 is a potentially attractive target for the immunotherapy of HL.
基金Supported by The National Institutes of Health to Luo Y,No.RO1DK066079
文摘AIM: To investigate the role of regulatory T (Treg) cells in CD4^+ T cell-mediated bladder autoimmune infammation. METHODS: Urothelium-ovalbumin (URO-OVA)/OT-II mice, a double transgenic line that expresses the membrane form of the model antigen (Ag) OVA as a self-Ag on the urothelium and the OVA-specific CD4^+ T cell receptor specifc for the I-Ab/OVA323-339 epitope in the periphery, were developed to provide an autoimmune environment for investigation of the role of Treg cells in bladder autoimmune infammation. To facilitate Treg cell analysis, we further developed URO-OVA^GFP-Foxp3/OT-II mice, a derived line of URO-OVA/OT-II mice that express the green fuorescent protein (GFP)-forkhead box protein P3 (Foxp3) fusion protein. RESULTS: URO-OVA/OT-II mice failed to develop bladder infammation despite the presence of autoreactive CD4^+ T cells. By monitoring GFP-positive cells, bladder infltration of CD4^+ Treg cells was observed in URO-OVA^GFP-Foxp3/OT-II mice. The infiltrating Treg cells were functionally active and expressed Treg cell effector molecule as well as marker mRNAs including transforming growth factor-β, interleukin (IL)-10, fibrinogen-like protein 2, and glucocorticoid-induced tumor necrosis factor receptor (GITR). Studies further revealed that Treg cells from URO-OVA^GFP-Foxp3/OT-II mice were suppressive and inhibited autoreactive CD4^+ T cell proliferation and interferon (IFN)-g production in response to OVA Ag stimulation. Depletion of GITR-positive cells led to spontaneous development of bladder infammation and expression of inflammatory factor mRNAs for IFN-γ, IL-6, tumor necrosis factor-α and nerve growth factor in URO-OVA^GFP-Foxp3/OT-II mice. CONCLUSION: Treg cells specifc for bladder epithelial Ag play an important role in immunological homeostasis and the control of CD4^+ T cell-mediated bladder autoimmune infammation.
基金National Natural Science Foundation of China(No.82370164)Sanming Project of Medicine in Shenzhen(No.SZSM202011004)Shenzhen Science and Technology Innovation Commission(JCYJ20180307150419435 and JCYJ20210324123004011).
文摘Background:Chimeric antigen receptor T(CAR-T)cell therapy has achieved marked therapeutic success in ameliorating hematological malignancies.However,there is an extant void in the clinical guidelines concerning the most effective chemotherapy regimen prior to chimeric antigen receptor T(CAR-T)cell therapy,as well as the optimal timing for CAR-T cell infusion post-chemotherapy.Materials and Methods:We employed cell-derived tumor xenograft(CDX)murine models to delineate the optimal pre-conditioning chemotherapy regimen and timing for CAR-T cell treatment.Furthermore,transcriptome sequencing was implemented to identify the therapeutic targets and elucidate the underlying mechanisms governing the treatment regimen.Results:Our preclinical in vivo evaluation determined that a combination of cyclophosphamide and fludarabine,followed by the infusion of CD19 CAR-T cells five days subsequent to the chemotherapy,exerts the most efficacious therapeutic effect in B-cell hematological malignancies.Concurrently,RNA-seq data indicated that the therapeutic efficacy predominantly perturbs tumor cell metabolism,primarily through the inhibition of key mitochondrial targets,such as C-Jun Kinase enzyme(C-JUN).Conclusion:In summary,the present study offers critical clinical guidance and serves as an authoritative reference for the deployment of CD19 CAR-T cell therapy in the treatment of B-cell hematological malignancies.
基金supported by fellowships from NJCCR to YT(DCHS20PPC024)and ZC(COCR23PDF017)and grants from the Ludwig Foundation,Brewster Foundation,American Cancer Society,Breast Cancer Research Foundation and Susan G.Komen Foundation to YK.All figures were made in BioRender.
文摘Dysregulation of lipid metabolism is a key characteristic of the tumor microenvironment,where tumor cells utilize lipids for proliferation,survival,metastasis,and evasion of immune surveillance.Lipid metabolism has become a critical regulator of CD8+T-cell-mediated antitumor immunity,with excess lipids in the tumor microenvironment impeding CD8+T-cell activities.Considering the limited efficacy of immunotherapy in many solid tumors,targeting lipid metabolism to enhance CD8+T-cell effector functions could significantly improve immunotherapy outcomes.In this review,we examine recent findings on how lipid metabolic processes,including lipid uptake,synthesis,and oxidation,regulate CD8+T cells within tumors.We also assessed the impact of different lipids on CD8+T-cell-mediated antitumor immunity,with a particular focus on how lipid metabolism affects mitochondrial function in tumor-infiltrating CD8+T cells.Furthermore,as cancer is a systemic disease,we examined systemic factors linking lipid metabolism to CD8+T-cell effector function.Finally,we summarize current therapeutic approaches that target lipid metabolism to increase antitumor immunity and enhance immunotherapy.Understanding the molecular and functional interplay between lipid metabolism and CD8+T cells offers promising therapeutic opportunities for cancer treatment.
文摘目的 探讨CD15抗原和组织蛋白酶D(Cath-D)在食管癌的表达意义及其相互关系。 方法 应用微波-LSAB免疫组化法,观察65例食管癌组织(男46例,女19例;平均年龄54岁;均为鳞癌)中CD15和Cath-D的表达阳性率及其相互关系。 结果 食管癌CD15和CD阳性率分别为58%(38/65例)和65%(42/65例);食管癌CD15和Cath-D表达与性别、年龄、肿瘤部位、大体类型及肿瘤大小无关(P>0.05)。CD15和Cath-D表达阳性率:鳞癌Ⅲ级(88%,14/16 vs 100%,16/16)均显著高于鳞癌Ⅰ级(43%,6/14 vs 50%,7/14)和鳞癌Ⅱ级(51%,18/35 vs 54%,19/35,P<0.05);外膜层浸润(74%,20/27 vs82%,22/27)显著高于肌层浸润(47%,18/38 vs 53%,20/38,P<0.05);有淋巴结转移组(72%,26/36 vs 78%,28/38)显著高于无淋巴结转移组(41%,12/29 vs 48%、14/29,P<0.025);死亡组(70%,31/44 vs 77%,34/44)显著高于五年生存组(33%,7/21 vs 38%,8/21,P<0.01)。CD15阳性的肿瘤Cath-D阳性率显著高于CD15阴性者(82%,31/38 vs41%,11/27),CD15表达与Cath-D表达呈正相关(r=0.42,P<0.01)。 结论 检测CD15和Cath-D表达对判断食管癌恶性程度、预测其侵袭转移趋势和预后及指导治疗有重要意义。食管癌CD15与Cath-D表达具有相互协同作用可能。