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[PMID]: 29381830
[Au] Autor:Sioud M
[Ad] Address:Department of Cancer Immunology, Oslo University Hospital, The Norwegian Radium Hospital, Montebello, Oslo, Norway.
[Ti] Title:T-cell cross-reactivity may explain the large variation in how cancer patients respond to checkpoint inhibitors.
[So] Source:Scand J Immunol;87(3), 2018 Mar.
[Is] ISSN:1365-3083
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:The therapeutic use of the immune system to specifically attack tumours has been a long-standing vision among tumour immunologists. Recently, the use of checkpoint inhibitors to turn-off immunosuppressive signals has proven to be effective in enhancing T-cell reactivity against patient-specific neoantigens, resulting from somatic mutations. Several of the identified T-cell epitopes share similarity with common bacterial and viral antigens, suggesting the involvement of pre-existing microbial cross-reactive T cells in rapid and durable tumour regression seen in some patients. This notion of T-cell cross-reactivity is further supported by the findings that intestinal bacteria can influence checkpoint-blockade therapy. Moreover, early data indicate the presence of such T cells in long-term survival breast cancer patients. This review highlights the main challenges for cancer immunotherapy and discusses the potential contribution of T-cell cross-reactivity in cancer immunotherapy and whether it can be used as a biomarker to predict the responsiveness to checkpoint inhibitors.
[Mh] MeSH terms primary: Cross Reactions/immunology
Immunotherapy/methods
Neoplasms/immunology
Neoplasms/therapy
T-Lymphocytes/immunology
[Mh] MeSH terms secundary: Antigens, Bacterial/immunology
Antigens, Neoplasm/immunology
Antigens, Viral/immunology
Biomarkers, Tumor/immunology
CTLA-4 Antigen/antagonists & inhibitors
Dendritic Cells/immunology
Epitopes, T-Lymphocyte/immunology
Humans
Lymphocyte Activation/immunology
Programmed Cell Death 1 Receptor/antagonists & inhibitors
Receptors, Immunologic/antagonists & inhibitors
[Pt] Publication type:JOURNAL ARTICLE; REVIEW
[Nm] Name of substance:0 (Antigens, Bacterial); 0 (Antigens, Neoplasm); 0 (Antigens, Viral); 0 (Biomarkers, Tumor); 0 (CTLA-4 Antigen); 0 (Epitopes, T-Lymphocyte); 0 (PDCD1 protein, human); 0 (Programmed Cell Death 1 Receptor); 0 (Receptors, Immunologic); 0 (TIGIT protein, human)
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[Js] Journal subset:IM
[Da] Date of entry for processing:180131
[St] Status:MEDLINE
[do] DOI:10.1111/sji.12643

  2 / 25179 MEDLINE  
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[PMID]: 29520563
[Au] Autor:Uccella S; La Rosa S; Volante M; Papotti M
[Ad] Address:Unit of Pathology, Department of Medicine and Surgery, University of Insubria, Varese, Italy.
[Ti] Title:Immunohistochemical Biomarkers of Gastrointestinal, Pancreatic, Pulmonary, and Thymic Neuroendocrine Neoplasms.
[So] Source:Endocr Pathol;, 2018 Mar 09.
[Is] ISSN:1559-0097
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Neuroendocrine neoplasms (NENs) are a heterogeneous group of epithelial neoplastic proliferations that irrespective of their primary site share features of neural and endocrine differentiation including the presence of secretory granules, synaptic-like vesicles, and the ability to produce amine and/or peptide hormones. NENs encompass a wide spectrum of neoplasms ranging from well-differentiated indolent tumors to highly aggressive poorly differentiated neuroendocrine carcinomas. Most cases arise in the digestive system and in thoracic organs, i.e., the lung and thymus. A correct diagnostic approach is crucial for the management of patients with both digestive and thoracic NENs, because their high clinical and biological heterogeneity is related to their prognosis and response to therapy. In this context, immunohistochemistry represents an indispensable diagnostic tool that pathologists need to use for the correct diagnosis and classification of such neoplasms. In addition, immunohistochemistry is also useful in identifying prognostic and theranostic markers. In the present article, the authors will review the role of immunohistochemistry in the routine workup of digestive and thoracic NENs.
[Pt] Publication type:JOURNAL ARTICLE; REVIEW
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:Publisher
[do] DOI:10.1007/s12022-018-9522-y

  3 / 25179 MEDLINE  
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[PMID]: 28922789
[Au] Autor:Mlecnik B; Van den Eynde M; Bindea G; Church SE; Vasaturo A; Fredriksen T; Lafontaine L; Haicheur N; Marliot F; Debetancourt D; Pairet G; Jouret-Mourin A; Gigot JF; Hubert C; Danse E; Dragean C; Carrasco J; Humblet Y; Valge-Archer V; Berger A; Pagès F; Machiels JP; Galon J
[Ad] Address:Laboratory of Integrative Cancer Immunology, INSERM, UMRS1138, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, UMRS1138, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMRS1138, Centre de Recherche des Cordeliers, Paris, France; Inovarion, Paris, France; Department of Medic
[Ti] Title:Comprehensive Intrametastatic Immune Quantification and Major Impact of Immunoscore on Survival.
[So] Source:J Natl Cancer Inst;110(1), 2018 Jan 01.
[Is] ISSN:1460-2105
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Background: This study assesses how the metastatic immune landscape is impacting the response to treatment and the outcome of colorectal cancer (CRC) patients. Methods: Complete curative resection of metastases (n = 441) was performed for two patient cohorts (n = 153). Immune densities were quantified in the center and invasive margin of all metastases. Immunoscore and T and B cell (TB) score were analyzed in relation to radiological and pathological responses and patient's disease-free (DFS) and overall survival (OS) using multivariable Cox proportional hazards models. All statistical tests were two-sided. Results: The spatial distribution of immune cells within metastases was nonuniform. Patients, as well as metastases of the same patient, had variable immune infiltrates and response to therapy. A beneficial response was statistically significantly associated with increased immune densities. Among all metastases, Immunoscore (I) and TB score evaluated in the least immune-infiltrated metastases were the strongest predictors for DFS and OS (five-year follow-up, Immunoscore: I 3-4: DFS rate = 27.9%, 95% CI = 15.2 to 51.3; vs I 0-1-2: DFS rate = 12.3%, 95% CI = 4.9 to 30.6; HR = 0.45, 95% CI = 0.28 to 0.70, P = .02; I 3-4: OS rate = 64.6%, 95% CI = 46.6 to 89.6; vs I 0-1-2: OS rate = 32.5%, 95% CI = 17.2 to 61.4; HR = 0.32, 95% CI = 0.15 to 0.66, P = .001, C-index = 65.9%; five-year follow-up, TB score: TB 3-4: DFS rate = 25.7%, 95% CI = 14.2 to 46.6; vs TB 0-1-2: DFS rate = 5.0%, 95% CI = 0.8 to 32.4; HR = 0.36, 95% CI = 0.22 to 0.57, P < .001; TB 3-4: OS rate = 63.7%, 95% CI = 46.4 to 87.5; vs TB 0-1-2: OS rate: 21.4%, 95% CI = 9.2 to 49.8; HR = 0.25, 95% CI = 0.12 to 0.51, P < .001, C-index = 67.8%). High TB score and Immunoscore patients had a median survival of 70.5 months, while low patients survived only 25.1 to 38.3 months. Nonresponding patients with high-immune infiltrates had prolonged DFS (HR = 0.28, 95% CI = 0.15 to 0.52, P = .001) and OS (HR = 0.25, 95% CI = 0.1 to 0.62, P = .001). The immune parameters remained the only statistically significant prognostic factor associated with DFS and OS in multivariable analysis (P < .001), while response to treatment was not. Conclusions: Response to treatment and prolonged survival of metastatic CRC patients were statistically significantly associated with high-immune densities quantified into the least immune-infiltrated metastasis.
[Mh] MeSH terms primary: B-Lymphocytes
Colorectal Neoplasms/immunology
Liver Neoplasms/immunology
Lung Neoplasms/immunology
Lymphocytes, Tumor-Infiltrating
T-Lymphocytes
[Mh] MeSH terms secundary: Aged
Antigens, CD20/analysis
Antineoplastic Combined Chemotherapy Protocols/therapeutic use
B-Lymphocytes/chemistry
CD3 Complex/analysis
CD8-Positive T-Lymphocytes
Chemotherapy, Adjuvant
Colorectal Neoplasms/pathology
Colorectal Neoplasms/therapy
Disease-Free Survival
Follow-Up Studies
Forkhead Transcription Factors/analysis
Hepatectomy
Humans
Leukocyte Common Antigens/analysis
Liver Neoplasms/secondary
Liver Neoplasms/therapy
Lung Neoplasms/secondary
Lung Neoplasms/therapy
Lymphocyte Count
Metastasectomy
Middle Aged
Neoplasm Metastasis
Pneumonectomy
Preoperative Period
Response Evaluation Criteria in Solid Tumors
Survival Rate
T-Lymphocytes/chemistry
Tumor Microenvironment/immunology
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:0 (Antigens, CD20); 0 (CD3 Complex); 0 (FOXP3 protein, human); 0 (Forkhead Transcription Factors); EC 3.1.3.48 (Leukocyte Common Antigens)
[Em] Entry month:1709
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[Js] Journal subset:IM
[Da] Date of entry for processing:170920
[St] Status:MEDLINE
[do] DOI:10.1093/jnci/djx123

  4 / 25179 MEDLINE  
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[PMID]: 27777141
[Au] Autor:Politikos I; T Kim H; Karantanos T; Brown J; McDonough S; Li L; Cutler C; Antin JH; Ballen KK; Ritz J; Boussiotis VA
[Ad] Address:Hematology-Oncology and Cancer Biology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
[Ti] Title:Angiogenic Factors Correlate with T Cell Immune Reconstitution and Clinical Outcomes after Double-Unit Umbilical Cord Blood Transplantation in Adults.
[So] Source:Biol Blood Marrow Transplant;23(1):103-112, 2017 Jan.
[Is] ISSN:1523-6536
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Umbilical cord blood (UCB) is a valuable graft source for allogeneic hematopoietic stem cell transplantation (HSCT) in patients who lack adult donors. UCB transplantation (UCBT) in adults results in delayed immune reconstitution, leading to high infection-related morbidity and mortality. Angiogenic factors and markers of endothelial dysfunction have biologic and prognostic significance in conventional HSCT, but their role in UCBT has not been investigated. Furthermore, the interplay between angiogenesis and immune reconstitution has not been studied. Here we examined whether angiogenic cytokines, angiopoietin-1 (ANG-1) and vascular endothelial growth factor (VEGF), or markers of endothelial injury, thrombomodulin (TM) and angiopoietin-2 (ANG-2), associate with thymic regeneration as determined by T cell receptor excision circle (TREC) values and recovery of T cell subsets, as well as clinical outcomes in adult recipients of UCBT. We found that plasma levels of ANG-1 significantly correlated with the reconstitution of naive CD4 CD45RA and CD8 CD45RA T cell subsets, whereas plasma levels of VEGF displayed a positive correlation with CD4 CD45RO T cells and regulatory T cells and a weak correlation with TRECs. Assessment of TM and ANG-2 revealed a strong inverse correlation of both factors with naive T cells and TRECs. The angiogenic capacity of each patient's plasma, as determined by an in vitro angiogenesis assay, positively correlated with VEGF levels and with reconstitution of CD4 T cell subsets. Higher VEGF levels were associated with worse progression-free survival and higher risk of relapse, whereas higher levels of TM were associated with chronic graft-versus-host disease and nonrelapse mortality. Thus, angiogenic factors may serve as valuable markers associated with T cell reconstitution and clinical outcomes after UCBT.
[Mh] MeSH terms primary: Angiogenesis Inducing Agents/blood
Cord Blood Stem Cell Transplantation/standards
Hematologic Neoplasms/therapy
Immune Reconstitution/immunology
[Mh] MeSH terms secundary: Adult
Aged
Angiopoietin-1/blood
Angiopoietin-2/blood
Biomarkers/blood
Cord Blood Stem Cell Transplantation/methods
Disease-Free Survival
Female
Graft vs Host Disease
Humans
Male
Middle Aged
Receptors, Antigen, T-Cell
Recurrence
T-Lymphocyte Subsets/immunology
T-Lymphocytes/immunology
Thrombomodulin/blood
Treatment Outcome
Vascular Endothelial Growth Factor A/blood
Young Adult
[Pt] Publication type:CLINICAL TRIAL, PHASE II; JOURNAL ARTICLE
[Nm] Name of substance:0 (Angiogenesis Inducing Agents); 0 (Angiopoietin-1); 0 (Angiopoietin-2); 0 (Biomarkers); 0 (Receptors, Antigen, T-Cell); 0 (Thrombomodulin); 0 (Vascular Endothelial Growth Factor A)
[Em] Entry month:1802
[Cu] Class update date: 180307
[Lr] Last revision date:180307
[Js] Journal subset:IM
[Da] Date of entry for processing:161026
[St] Status:MEDLINE

  5 / 25179 MEDLINE  
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[PMID]: 29360859
[Au] Autor:Zhou J; Bethune MT; Malkova N; Sutherland AM; Comin-Anduix B; Su Y; Baltimore D; Ribas A; Heath JR
[Ad] Address:NanoSystems Biology Cancer Center, California Institute of Technology, Pasadena, California, United States of America.
[Ti] Title:A kinetic investigation of interacting, stimulated T cells identifies conditions for rapid functional enhancement, minimal phenotype differentiation, and improved adoptive cell transfer tumor eradication.
[So] Source:PLoS One;13(1):e0191634, 2018.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:For adoptive cell transfer (ACT) immunotherapy of tumor-reactive T cells, an effective therapeutic outcome depends upon cell dose, cell expansion in vivo through a minimally differentiated phenotype, long term persistence, and strong cytolytic effector function. An incomplete understanding of the biological coupling between T cell expansion, differentiation, and response to stimulation hinders the co-optimization of these factors. We report on a biophysical investigation of how the short-term kinetics of T cell functional activation, through molecular stimulation and cell-cell interactions, competes with phenotype differentiation. T cells receive molecular stimulation for a few minutes to a few hours in bulk culture. Following this priming period, the cells are then analyzed at the transcriptional level, or isolated as single cells, with continuing molecular stimulation, within microchambers for analysis via 11-plex secreted protein assays. We resolve a rapid feedback mechanism, promoted by T cell-T cell contact interactions, which strongly amplifies T cell functional performance while yielding only minimal phenotype differentiation. When tested in mouse models of ACT, optimally primed T cells lead to complete tumor eradication. A similar kinetic process is identified in CD8+ and CD4+ T cells collected from a patient with metastatic melanoma.
[Mh] MeSH terms primary: Adoptive Transfer
Immunophenotyping
Neoplasms/therapy
T-Lymphocytes/immunology
[Mh] MeSH terms secundary: Animals
Female
Flow Cytometry
Heterografts
Humans
Lymphocyte Activation
Mice
Mice, Inbred C57BL
Mice, Transgenic
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Entry month:1802
[Cu] Class update date: 180226
[Lr] Last revision date:180226
[Js] Journal subset:IM
[Da] Date of entry for processing:180124
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191634

  6 / 25179 MEDLINE  
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[PMID]: 29182373
[Au] Autor:Nakajo M; Jinguji M; Shinaji T; Nakajo M; Aoki M; Tani A; Sato M; Yoshiura T
[Ad] Address:1 Department of Radiology, Kagoshima University, Graduate School of Medical and Dental Sciences , Kagoshima , Japan.
[Ti] Title:Texture analysis of F-FDG PET/CT for grading thymic epithelial tumours: usefulness of combining SUV and texture parameters.
[So] Source:Br J Radiol;91(1083):20170546, 2018 Feb.
[Is] ISSN:1748-880X
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:OBJECTIVE: To retrospectively investigate the standardized uptake value (SUV)-related and heterogeneous texture parameters individually and in combination for differentiating between low- and high-risk Fluorone-fludeoxyglucose ( F-FDG)-avid thymic epithelial tumours (TETs) with positron emission tomography (PET)/CT. METHODS: SUV-related and 6 texture parameters (entropy, homogeneity, dissimilarity, intensity variability, size-zone variability and zone percentage) were compared between 11 low-risk and 23 high-risk TETs (metabolic tumour volume >10.0 cm and SUV ≥2.5). Diagnostic performance was evaluated by receiver operating characteristic analysis. The diagnostic value of combining SUV and texture parameters was examined by a scoring system. RESULTS: High-risk TETs were significantly higher in SUVmax (p = 0.022), entropy (p = 0.038), intensity variability (p = 0.041) and size-zone variability (p = 0.045) than low-risk TETs. Diagnostic accuracies of these 4 parameters, dissimilarity and zone percentage which also showed significance in receiver operating characteristic analysis ranged between 64.7 and 73.5% without significant differences in AUC (range; 0.71 to 0.75) (p ≥ 0.05 each). Each parameter was scored as 0 (negative for high-risk) or 1 (positive for high-risk) according to each threshold criterion, then scores were summed [0 or 1 for low-risk TETs (median; 1); ≥2 for high-risk TETs (median; 4)]. The sensitivity, specificity and accuracy of detecting high-risk TETs were 100, 81.8 and 94.1%, respectively, with an AUC of 0.99. CONCLUSION: The diagnostic performances of individual SUVmax and texture parameters were relatively low. However, combining these parameters can significantly increase diagnostic performance when differentiating between relatively large low- and high-risk F-FDG-avid TETs. Advances in knowledge: Combined use of SUVmax and texture parameters can significantly increase the diagnostic performance when differentiating between low- and high-risk TETs.
[Mh] MeSH terms primary: Neoplasms, Glandular and Epithelial/diagnostic imaging
Neoplasms, Glandular and Epithelial/pathology
Positron Emission Tomography Computed Tomography/methods
Thymus Neoplasms/diagnostic imaging
Thymus Neoplasms/pathology
[Mh] MeSH terms secundary: Adult
Aged
Aged, 80 and over
Female
Fluorodeoxyglucose F18
Humans
Male
Middle Aged
Neoplasm Grading
Neoplasm Staging
Radiopharmaceuticals
Retrospective Studies
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:0 (Radiopharmaceuticals); 0Z5B2CJX4D (Fluorodeoxyglucose F18)
[Em] Entry month:1802
[Cu] Class update date: 180226
[Lr] Last revision date:180226
[Js] Journal subset:AIM; IM
[Da] Date of entry for processing:171129
[St] Status:MEDLINE
[do] DOI:10.1259/bjr.20170546

  7 / 25179 MEDLINE  
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[PMID]: 29411013
[Au] Autor:Hampton T
[Ti] Title:Gut Microbes May Shape Response to Cancer Immunotherapy.
[So] Source:JAMA;319(5):430-431, 2018 Feb 06.
[Is] ISSN:1538-3598
[Cp] Country of publication:United States
[La] Language:eng
[Mh] MeSH terms primary: Gastrointestinal Microbiome/physiology
Immunotherapy
Neoplasms/therapy
Programmed Cell Death 1 Receptor/antagonists & inhibitors
T-Lymphocytes/immunology
[Mh] MeSH terms secundary: CD8-Positive T-Lymphocytes/immunology
Humans
Neoplasms/microbiology
T-Lymphocytes, Regulatory/immunology
Verrucomicrobia
[Pt] Publication type:NEWS
[Nm] Name of substance:0 (Programmed Cell Death 1 Receptor)
[Em] Entry month:1802
[Cu] Class update date: 180215
[Lr] Last revision date:180215
[Js] Journal subset:AIM; IM
[Da] Date of entry for processing:180208
[St] Status:MEDLINE
[do] DOI:10.1001/jama.2017.12857

  8 / 25179 MEDLINE  
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[PMID]: 29195073
[Au] Autor:Topper MJ; Vaz M; Chiappinelli KB; DeStefano Shields CE; Niknafs N; Yen RC; Wenzel A; Hicks J; Ballew M; Stone M; Tran PT; Zahnow CA; Hellmann MD; Anagnostou V; Strissel PL; Strick R; Velculescu VE; Baylin SB
[Ad] Address:Department of Oncology, The Johns Hopkins School of Medicine, The Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21287, USA; The Graduate Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
[Ti] Title:Epigenetic Therapy Ties MYC Depletion to Reversing Immune Evasion and Treating Lung Cancer.
[So] Source:Cell;171(6):1284-1300.e21, 2017 Nov 30.
[Is] ISSN:1097-4172
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Combining DNA-demethylating agents (DNA methyltransferase inhibitors [DNMTis]) with histone deacetylase inhibitors (HDACis) holds promise for enhancing cancer immune therapy. Herein, pharmacologic and isoform specificity of HDACis are investigated to guide their addition to a DNMTi, thus devising a new, low-dose, sequential regimen that imparts a robust anti-tumor effect for non-small-cell lung cancer (NSCLC). Using in-vitro-treated NSCLC cell lines, we elucidate an interferon α/ß-based transcriptional program with accompanying upregulation of antigen presentation machinery, mediated in part through double-stranded RNA (dsRNA) induction. This is accompanied by suppression of MYC signaling and an increase in the T cell chemoattractant CCL5. Use of this combination treatment schema in mouse models of NSCLC reverses tumor immune evasion and modulates T cell exhaustion state towards memory and effector T cell phenotypes. Key correlative science metrics emerge for an upcoming clinical trial, testing enhancement of immune checkpoint therapy for NSCLC.
[Mh] MeSH terms primary: Carcinoma, Non-Small-Cell Lung/therapy
Drug Therapy, Combination
Lung Neoplasms/therapy
Tumor Escape/drug effects
[Mh] MeSH terms secundary: Animals
Antigen Presentation/drug effects
Antineoplastic Agents/therapeutic use
Azacitidine/therapeutic use
Carcinoma, Non-Small-Cell Lung/genetics
Carcinoma, Non-Small-Cell Lung/immunology
Cell Line, Tumor
Histone Deacetylase Inhibitors/therapeutic use
Hydroxamic Acids/therapeutic use
Immunotherapy
Lung Neoplasms/genetics
Lung Neoplasms/immunology
Mice
T-Lymphocytes/immunology
Transcriptome
Tumor Microenvironment
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:0 (Antineoplastic Agents); 0 (Histone Deacetylase Inhibitors); 0 (Hydroxamic Acids); M801H13NRU (Azacitidine); Z02132R2QQ (givinostat hydrochloride)
[Em] Entry month:1712
[Cu] Class update date: 180214
[Lr] Last revision date:180214
[Js] Journal subset:IM
[Da] Date of entry for processing:171202
[St] Status:MEDLINE

  9 / 25179 MEDLINE  
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[PMID]: 29276997
[Au] Autor:Chae YK; Galvez C; Anker JF; Iams WT; Bhave M
[Ad] Address:Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA. Electronic address: young.chae@northwestern.edu.
[Ti] Title:Cancer immunotherapy in a neglected population: The current use and future of T-cell-mediated checkpoint inhibitors in organ transplant patients.
[So] Source:Cancer Treat Rev;63:116-121, 2018 Feb.
[Is] ISSN:1532-1967
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:Although the indications for immune checkpoint inhibitors continue to grow, organ transplant recipients with advanced malignancies have been largely excluded from clinical trials testing the safety and efficacy of these therapies given their need for chronic immunosuppression and the risk of allograft rejection. With the rapid growth of transplant medicine and the increased risk of malignancy associated with chronic immunosuppression, it is critical that we systematically analyze the available data describing immune checkpoint blockade in the organ transplant population. Herein we provide a current and comprehensive review of cases in which immune checkpoint blockade was used on organ transplant recipients. Furthermore, we discuss the differences in efficacy and risk of allograft rejection between CTLA-4 and PD-1 inhibitors and make recommendations based on the limited available clinical data. We also discuss the future of immune checkpoint blockade in this subpopulation and explore the emerging data of promising combination therapies with mTOR, BRAF/MEK, and BTK/ITK inhibitors. Further clinical experience and larger clinical trials involving immune checkpoint inhibitors, whether as monotherapies or combinatorial therapies, will help develop regimens that optimize anti-tumor response and minimize the risk of allograft rejection in organ transplant patients.
[Mh] MeSH terms primary: Neoplasms/immunology
Neoplasms/therapy
T-Lymphocytes/immunology
Transplants/immunology
[Mh] MeSH terms secundary: Animals
Humans
Immunotherapy/methods
Transplant Recipients
[Pt] Publication type:JOURNAL ARTICLE; REVIEW
[Em] Entry month:1802
[Cu] Class update date: 180209
[Lr] Last revision date:180209
[Js] Journal subset:IM
[Da] Date of entry for processing:171226
[St] Status:MEDLINE

  10 / 25179 MEDLINE  
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[PMID]: 28466469
[Au] Autor:Zhao XY; Luo XY; Yu XX; Zhao XS; Han TT; Chang YJ; Huo MR; Xu LP; Zhang XH; Liu KY; Li D; Jiang ZF; Huang XJ
[Ad] Address:Peking University People's Hospital, Peking University Institute of Haematology, Beijing Key Laboratory of Haematopoietic Stem Cell Transplantation, Beijing, China.
[Ti] Title:Recipient-donor KIR ligand matching prevents CMV reactivation post-haploidentical T cell-replete transplantation.
[So] Source:Br J Haematol;177(5):766-781, 2017 06.
[Is] ISSN:1365-2141
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Licensed natural killer (NK) cells have been demonstrated to have anti-cytomegalovirus (CMV) activity. We prospectively analysed the human leucocyte antigen typing of donor-recipient pairs and the killer cell immunoglobulin-like receptor (KIR) typing of donors for 180 leukaemia patients to assess the predictive roles of licensed NK cells on CMV reactivation post-T-cell-replete haploidentical stem cell transplantation. Multivariate analysis showed that donor-recipient KIR ligand graft-versus-host or host-versus-graft direction mismatch was associated with increased refractory CMV infection (Hazard ratio = 2·556, 95% confidence interval, 1·377-4·744, P = 0·003) post-transplantation. Donor-recipient KIR ligand matching decreased CMV reactivation [51·65% (46·67, 56·62%) vs. 75·28% (70·87, 79·69%), P = 0·012], refractory CMV infection [17·58% (13·77, 21·40%) vs. 35·96% (31·09, 40·82%), P = 0·004] and CMV disease [3·30% (1·51, 5·08%) vs. 11·24% (8·04, 14·43%), P = 0·024] by day 100 post-transplantation. In addition, the percentage of γ-interferon expression on donor-derived NK cells was significantly higher in the recipients among the recipient-donor pairs with a KIR ligand match compared with that in the recipients among the pairs with a KIR ligand graft-versus-host or host-versus-graft direction mismatch on days 30 and 100 post-transplantation (P = 0·036 and 0·047, respectively). These findings have suggested that donor-recipient KIR ligand matching might promote the NK cell licensing process, thereby increasing NK cell-mediated protection against CMV reactivation.
[Mh] MeSH terms primary: Cytomegalovirus Infections/prevention & control
T-Lymphocytes/transplantation
[Mh] MeSH terms secundary: Adolescent
Adult
Child
Cytomegalovirus/physiology
Female
Hematologic Neoplasms/therapy
Histocompatibility Testing/methods
Humans
Killer Cells, Natural/immunology
Killer Cells, Natural/physiology
Male
Middle Aged
Prospective Studies
Receptors, KIR/genetics
Receptors, KIR/immunology
Stem Cell Transplantation/methods
Transplant Recipients
Transplantation Conditioning/methods
Virus Activation/genetics
Virus Activation/immunology
Young Adult
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Name of substance:0 (KIR2DS2 protein, human); 0 (Receptors, KIR)
[Em] Entry month:1708
[Cu] Class update date: 180209
[Lr] Last revision date:180209
[Js] Journal subset:IM
[Da] Date of entry for processing:170504
[St] Status:MEDLINE
[do] DOI:10.1111/bjh.14622


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