المؤلفون: Ryusaku Matsumoto, Masaaki Yamamoto, Genzo Iguchi, Shin Urai, Hidenori Fukuoka, Wataru Ogawa, Kentaro Suda, Hiroki Shichi, Keitaro Kanie, Yutaka Takahashi, Hironori Bando, Yasunori Fujita

المصدر: Cancer Immunology, Immunotherapy

مصطلحات موضوعية: Male, Cancer Research, Pro-Opiomelanocortin, Paraneoplastic Syndromes, Programmed Cell Death 1 Receptor, Autoimmunity, Hypopituitarism, Immune checkpoint inhibitor, medicine.disease_cause, B7-H1 Antigen, Mice, 0302 clinical medicine, Neoplasms, Immunology and Allergy, CTLA-4 Antigen, Corticotrophs, Immune Checkpoint Inhibitors, Aged, 80 and over, biology, Middle Aged, Oncology, 030220 oncology & carcinogenesis, Paraneoplastic syndrome, Female, Original Article, Immunotherapy, Antibody, hormones, hormone substitutes, and hormone antagonists, Adult, endocrine system, Hypophysitis, Immunology, 030209 endocrinology & metabolism, Adrenocorticotropic hormone, 03 medical and health sciences, Antigen, medicine, Animals, Humans, Aged, Retrospective Studies, business.industry, medicine.disease, biology.protein, Ectopic expression, Corticotropic cell, business, Adrenal Insufficiency

الوصف: Background Immune checkpoint inhibitors (ICIs) as a cancer immunotherapy have emerged as a treatment for multiple advanced cancer types. Because of enhanced immune responses, immune-related adverse events (irAEs), including endocrinopathies such as hypophysitis, have been associated with the use of ICIs. Most underlying mechanisms of ICI-related hypophysitis remain unclear, especially for programmed cell death-1 (PD-1)/PD-1 ligand 1 (PD-L1) inhibitors. We hypothesized that ICI-related hypophysitis is associated with paraneoplastic syndrome caused by ectopic expression of pituitary-specific antigens. Methods Twenty consecutive patients with ICI-related hypophysitis between 2017 and 2019 at Kobe University Hospital were retrospectively analyzed. Circulating anti-pituitary antibodies were detected using immunofluorescence staining and immunoblotting. Ectopic expression of pituitary autoantigens in tumor specimens was also examined. Results Eighteen patients were treated with PD-1/PD-L1 inhibitors, and two were treated with a combination of cytotoxic T-lymphocyte antigen-4 (CTLA-4) and PD-1 inhibitors. All patients showed adrenocorticotropic hormone (ACTH) deficiency and additionally, three showed thyroid-stimulating hormone (TSH) deficiency, and one showed gonadotropin-releasing hormone (GnRH) deficiency. Among these patients, three exhibited anti-pituitary antibodies, two with anti-corticotroph antibody and one with anti-somatotroph antibody. Interestingly, the anti-corticotroph antibody recognized proopiomelanocortin (POMC) and those two patients exhibited ectopic ACTH expression in the tumor, while the patients without anti-corticotroph antibody did not. Conclusions We demonstrated 10% of PD-1/PD-L1 inhibitors-related hypophysitis were associated with the autoimmunity against corticotrophs and maybe caused as a form of paraneoplastic syndrome, in which ectopic expression of ACTH in the tumor was observed. It is also suggested that the pathophysiology is heterogenous in ICI-related hypophysitis.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3acc181a81511e7fe6b828ea748faa32Test
https://hdl.handle.net/20.500.14094/90008773Test

المؤلفون: Jie Li, Longteng Jin, Shanshan Huang, Chuanhua Gao, Changzhong Jin

المصدر: Molecular Medicine Reports

مصطلحات موضوعية: Adult, CD4-Positive T-Lymphocytes, Male, 0301 basic medicine, Cancer Research, HIV Infections, HIV-1 DNA, Biology, Biochemistry, Peripheral blood mononuclear cell, Gene Expression Regulation, Enzymologic, elite controllers, immune activation, SAM Domain and HD Domain-Containing Protein 1, 03 medical and health sciences, 0302 clinical medicine, Genetics, Humans, sterile α motif and histidine/aspartic acid domain-containing protein 1, Molecular Biology, Gene, Regulation of gene expression, Oncogene, Interferon-alpha, Articles, Middle Aged, Viral Load, Cell cycle, Reverse transcriptase, 030104 developmental biology, Anti-Retroviral Agents, Oncology, Apoptosis, 030220 oncology & carcinogenesis, DNA, Viral, Immunology, HIV-1, Leukocytes, Mononuclear, RNA, Viral, Molecular Medicine, Female, SAMHD1

الوصف: Sterile α motif and histidine/aspartic acid domain-containing protein 1 (SAMHD1) can inhibit reverse transcription of human immunodeficiency virus-1 (HIV-1) by hydrolyzing intracellular deoxy-ribonucleoside triphosphate. However, its role in HIV-1 disease progression has not been extensively studied. To study the impacts of SAMHD1 on HIV-1 disease progression, especially on DNA levels, we investigated SAMHD1 levels in the peripheral blood of HIV-1 elite controllers (ECs), antiretroviral therapy (ART) naive viremic progressors (VPs) and patients with HIV-1 receiving ART (HIV-ARTs) compared with healthy controls. In addition, the present study analyzed the relationship between SAMHD1 and interferon-α, immune activation and HIV-1 DNA levels. The results of the present study demonstrated elevated SAMHD1 expression in the peripheral blood mononuclear cells of all patients withHIV-1, but higher SAMHD1 expression in the CD4+ T cells of only ECs compared with healthy controls. Immune activation was increased in the VPs and decreased in the ECs compared with healthy controls. Substantially lower HIV-1 DNA levels were identified in ECs compared with those in VPs and HIV-ARTs. SAMHD1 expression was associated with low levels of immune activation. No significant correlation was observed between SAMHD1 and HIV-1 DNA levels. Overall, the findings of the present study indicated that SAMHD1 was highly expressed in ECs, which may be associated with low immune activation levels, but was not directly related to HIV-1 DNA levels.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::779b8ae7dcad85cf36332ff19bee6b43Test
https://doi.org/10.3892/mmr.2020.11153Test

المؤلفون: Kyoko Arai, Takao Kamai, Akinori Nukui, Minoru Kobayashi, Hideo Yuki, Takahiro Narimatsu, Yoshitatsu Fukabori, Toshiki Kijima, Ken-Ichiro Yoshida, Hideyuki Abe, Tsunehito Kambara, Hironori Betsunoh, Masahiro Yashi

المصدر: Cancer Immunology, Immunotherapy

مصطلحات موضوعية: Male, Cancer Research, Lymphocyte, Kidney, Nephroureterectomy, B7-H1 Antigen, Immune tolerance, 0302 clinical medicine, Tumor Microenvironment, Neutrophil-to-lymphocyte ratio (NLR), Immunology and Allergy, Stage (cooking), Aged, 80 and over, 0303 health sciences, Univariate analysis, Middle Aged, Prognosis, Kidney Neoplasms, Progression-Free Survival, Programmed cell death 1 ligand 1 (PD-L1), medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Upper tract urothelial carcinoma (UTUC), Disease Progression, Immunohistochemistry, Female, Original Article, Tumor-infiltrating lymphocyte (TIL), Adult, Immunology, 03 medical and health sciences, Lymphocytes, Tumor-Infiltrating, medicine, Humans, Aged, Retrospective Studies, 030304 developmental biology, Carcinoma, Transitional Cell, Tumor microenvironment, Ureteral Neoplasms, Tumor-infiltrating lymphocytes, business.industry, Cancer, medicine.disease, Cancer research, Neoplasm Grading, Ureter, business, Follow-Up Studies

الوصف: Background Increased expression of programmed cell death 1 ligand 1 (PD-L1) by tumor cells is thought to be a mechanism through which solid cancers promote immune tolerance. However, the association between PD-L1 expression and the prognosis of upper urinary tract urothelial carcinoma (UTUC) remains unknown. Methods We examined immunohistochemical PD-L1 expression and the tumor-infiltrating lymphocyte density (TILD) in 79 patients with UTUC who underwent nephroureterectomy. We classified the tumors into four types based on the combination of PD-L1 expression and TILD, and studied the clinicopathological characteristics of these four tumor types. Results Elevated expression of PD-L1 by tumor cells and a higher TILD were associated with a worse histological grade, higher pT stage, and higher peripheral blood neutrophil-to-lymphocyte ratio. Elevated expression of PD-L1 by tumor cells, a higher TILD, and type I, III, or IV tumors with elevated expression of either PD-L1 or TILD showed a positive correlation with poorer differentiation and local invasion. These three variables were associated with shorter progression-free survival and overall survival in univariate analysis, but only the latter was an independent determinant according to multivariate analysis. The patients who had type II tumors with lower PD-L1 expression and a lower TILD showed more favorable survival than the other three groups. Conclusions These findings suggest that PD-L1 expression and TILs in the tumor microenvironment influence the progression of UTUC. Accordingly, it is important to understand the immunologic characteristics of the tumor microenvironment to develop more effective treatment strategies for this cancer.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2a089064114954a8996f5b69f009caefTest
https://doi.org/10.1007/s00262-020-02499-7Test

المؤلفون: William Rodin, Filip Ahlmanner, Elinor Bexe Lindskog, Yvonne Wettergren, Louis Szeponik, Kamil Kajetan Zajt, Marianne Quiding Järbrink, Patrik Sundström

المصدر: Cancer Immunology, Immunotherapy

مصطلحات موضوعية: Adult, Male, Cancer Research, Exhaustion, Immunology, Programmed Cell Death 1 Receptor, Tim-3, Lymphocyte Activation, Mucosal-Associated Invariant T Cells, Flow cytometry, 03 medical and health sciences, 0302 clinical medicine, Immunity, Antigens, CD, Blocking antibody, PD-1, medicine, Tumor Microenvironment, Immunology and Allergy, Cytotoxic T cell, Humans, Secretion, Hepatitis A Virus Cellular Receptor 2, MAIT cell, 030304 developmental biology, Aged, Cell Proliferation, Aged, 80 and over, 0303 health sciences, Tumor microenvironment, CD39, medicine.diagnostic_test, Effector, Chemistry, Apyrase, Middle Aged, Colorectal cancer, In vitro, Phenotype, Oncology, Colonic Neoplasms, Cancer research, Cytokines, Original Article, Female, Biomarkers, 030215 immunology

الوصف: Mucosal-associated invariant T (MAIT) cells are unconventional T cells recognizing microbial metabolites, presented by the invariant MR1 protein. Upon activation, MAIT cells rapidly secrete cytokines and exert cytotoxic functions, and may thus be highly relevant also in tumor immunity. MAIT cells accumulate in colon tumors, but in contrast to other cytotoxic T cell subsets, their presence in tumors has been associated with worse patient outcome. Here we investigated if exhaustion may contribute to reduced anti-tumor immunity by MAIT cells. Freshly isolated lymphocytes from colon tumors, unaffected tissue and blood from the same patients were analyzed by flow cytometry to detect MAIT cells with effector functions that are relevant for tumor immunity, and their expression of inhibitory receptors and other exhaustion markers. Our studies show that MAIT cells with a PD-1highTim-3+CD39+ terminally exhausted phenotype and an increased proliferation accumulate in colon tumors. The exhausted MAIT cells have reduced polyfunctionality with regard to production of important anti-tumor effector molecules, and blocking antibodies to PD-1 partly improved activation of tumor-infiltrating MAIT cells in vitro. We conclude that the tumor microenvironment leads to exhaustion not only of conventional T cells, but also MAIT cells, and that checkpoint blockade therapy may be useful also to reinvigorate tumor-infiltrating MAIT cells. Supplementary Information The online version contains supplementary material available at 10.1007/s00262-021-02939-y.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a8846e11fd7e69e73f9cd68dd02080acTest
http://europepmc.org/articles/PMC8571139Test

المؤلفون: Masanori Hayashi, Tetsuro Yamagishi, Chihaya Imai, Hajime Umezu, Takashi Ariizumi, Yudai Murayama, Akira Ogose, Naoki Oike, Hiroyuki Kawashima, Hiroshi Hatano, Naoto Endo

المصدر: Cancer Immunology, Immunotherapy

مصطلحات موضوعية: Male, Cancer Research, Pathology, medicine.medical_treatment, Liposarcomas, B7-H1 Antigen, 0302 clinical medicine, HLA Antigens, Tumor Microenvironment, Immunology and Allergy, Programmed death ligand 1, Aged, 80 and over, 0303 health sciences, Middle Aged, Prognosis, Immunohistochemistry, Liposarcoma, Myxoid, Progression-Free Survival, Oncology, 030220 oncology & carcinogenesis, Original Article, Female, Human leukocyte antigen I, Adult, medicine.medical_specialty, Adolescent, Tumor immune microenvironment, Immunology, Down-Regulation, Human leukocyte antigen, Liposarcoma, Pleomorphic Liposarcoma, 03 medical and health sciences, Young Adult, Lymphocytes, Tumor-Infiltrating, medicine, Humans, neoplasms, 030304 developmental biology, Aged, Myxoid liposarcoma, Tumor-infiltrating lymphocytes, business.industry, Macrophages, Histocompatibility Antigens Class I, Immunotherapy, medicine.disease, body regions, CD163+ macrophages, business, CD163

الوصف: The characteristics of the tumor immune microenvironment remains unclear in liposarcomas, and here we aimed to determine the prognostic impact of the tumor immune microenvironment across separate liposarcomas subtypes. A total of 70 liposarcoma patients with three subtypes: myxoid liposarcoma (n = 45), dedifferentiated liposarcoma (n = 17), and pleomorphic liposarcoma (n = 8) were enrolled. The presence of tumor infiltrating lymphocytes (CD4+ , CD8+ , FOXP3+ lymphocytes) and CD163+ macrophages and expression of HLA class I and PD-L1 were assessed by immunohistochemistry in the diagnostic samples; overall survival and progression-free survival were estimated from outcome data. For infiltrating lymphocytes and macrophages, dedifferentiated liposarcoma and pleomorphic liposarcoma patients had a significantly higher number than myxoid liposarcoma patients. While myxoid liposarcoma patients with a high number of macrophages were associated with worse overall and progression-free survival, dedifferentiated liposarcoma patients with high macrophage numbers showed a trend toward favorable prognosis. Expression of HLA class I was negative in 35 of 45 (77.8%) myxoid liposarcoma tumors, whereas all dedifferentiated liposarcoma and pleomorphic liposarcoma tumors expressed HLA class I. The subset of myxoid liposarcoma patients with high HLA class I expression had significantly poor overall and progression-free survival, while dedifferentiated liposarcoma patients with high HLA class I expression tended to have favorable outcomes. Only four of 17 (23.5%) dedifferentiated liposarcomas, two of eight (25%) pleomorphic liposarcomas, and no myxoid liposarcoma tumors expressed PD-L1. Our results demonstrate the unique immune microenvironment of myxoid liposarcomas compared to other subtypes of liposarcomas, suggesting that the approach for immunotherapy in liposarcomas should be based on subtype.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::80679c1ba2c44a0ce4ca344ffcd402aeTest
http://europepmc.org/articles/PMC8571150Test

المؤلفون: Bożena Cybulska-Stopa, Barbara Ziółkowska, Łukasz Galus, Tomasz Kubiatowski, Stanisław Kieszko, Karolina Piejko, Jacek Mackiewicz, Piotr Rutkowski, Anna Drosik-Kwaśniewska, Jacek Calik, Grażyna Kamińska-Winciorek, Marcin Ziętek, Anna M. Czarnecka, Renata Pacholczak-Madej, Paweł Rogala, Katarzyna Gajewska-Wicher, Rafał Suwiński, Janusz Rolski, Agata Sałek-Zań, Natasza Kempa-Kamińska

المصدر: Immunotherapy. 13:297-307

مصطلحات موضوعية: Adult, Male, Oncology, medicine.medical_specialty, Multivariate analysis, Drug-Related Side Effects and Adverse Reactions, medicine.medical_treatment, Programmed Cell Death 1 Receptor, Immunology, Pembrolizumab, Antibodies, Monoclonal, Humanized, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Humans, Immunology and Allergy, Medicine, 030212 general & internal medicine, Stage (cooking), Adverse effect, Immune Checkpoint Inhibitors, Melanoma, Aged, Retrospective Studies, Aged, 80 and over, business.industry, Immunotherapy, Middle Aged, Prognosis, medicine.disease, Progression-Free Survival, Survival Rate, Clinical trial, Nivolumab, Treatment Outcome, 030220 oncology & carcinogenesis, Female, Poland, business

الوصف: Aim: To evaluate treatment results in advanced/metastatic melanoma patients treated with anti-PD-1 immunotherapy in routine practice in oncology centers in Poland. Methods: Multicenter retrospective analysis included 499 patients with unresectable/metastatic (stage IIIC–IV) melanoma treated with anti-PD-1 in first-line therapy. Results: Estimated median overall survival (OS) and progression-free survival (PFS) were 19.9 and 7.9 months, respectively. Multivariate analysis confirmed that ECOG 0, no brain metastases, normal lactate dehydrogenase level and occurrence of immune-related adverse events (irAEs) were statistically significantly associated with improved OS and PFS. Any irAE occurred in 24% of patients. Grade 3 or Grade 4 irAEs occurred in 6% of patients. Conclusion: Analysis revealed a slightly worse OS in real-world treatment in comparison to clinical trials (KEYNOTE-006 and CheckMate 066). Polish population treatment results are similar to other studies of real-world data. PFS and ORR are similar in our research and clinical trials.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::75481f1f9c5cc0cca549a49f8bad084dTest
https://doi.org/10.2217/imt-2020-0217Test

المؤلفون: Kazuho Morichika, Shugo Sakihama, Hiroaki Masuzaki, Sawako Nakachi, Jun-Nosuke Uchihara, Kennosuke Karube, Shingo Nakayama, Kazuko Sakai, Satoko Morishima, Kazuto Nishio, Masaki Hayashi, Rumiko Saito, Takeaki Tomoyose, Takuya Fukushima, Megumi Miyara, Takashi Miyagi, Kazuiku Ohshiro

المصدر: Cancer Science

مصطلحات موضوعية: 0301 basic medicine, Genetics, Genomics and Proteomics, Male, Cancer Research, RHOA, Genotyping Techniques, Kaplan-Meier Estimate, Gene mutation, medicine.disease_cause, Genetic analysis, 0302 clinical medicine, Japan, immune system diseases, hemic and lymphatic diseases, Ethnicity, Leukemia-Lymphoma, Adult T-Cell, geographical mutation heterogeneity, Aged, 80 and over, Mutation, Human T-lymphotropic virus 1, biology, High-Throughput Nucleotide Sequencing, General Medicine, Gene Products, tax, Genetic Profile, Middle Aged, Prognosis, Leukemia, Oncology, 030220 oncology & carcinogenesis, Original Article, Female, Adult, integrated clinico‐genetic analysis, DNA Copy Number Variations, Polymorphism, Single Nucleotide, Adult T-cell leukemia/lymphoma, 03 medical and health sciences, PRDM1, medicine, Biomarkers, Tumor, adult T‐cell leukemia/lymphoma, Humans, Aged, human T‐cell leukemia virus type I, Original Articles, medicine.disease, tax subgroup, HTLV-I Infections, Lymphoma, 030104 developmental biology, Immunology, biology.protein, Follow-Up Studies

الوصف: Genetic alterations in adult T‐cell leukemia/lymphoma (ATLL), a T‐cell malignancy associated with HTLV‐1, and their clinical impacts, especially from the perspective of viral strains, are not fully elucidated. We employed targeted next‐generation sequencing and single nucleotide polymorphism array for 89 patients with ATLL in Okinawa, the southernmost islands in Japan, where the frequency of HTLV‐1 tax subgroup‐A (HTLV‐1‐taxA) is notably higher than that in mainland Japan, where most ATLL cases have HTLV‐1‐taxB, and compared the results with previously reported genomic landscapes of ATLL in mainland Japan and the USA. Okinawan patients exhibited similar mutation profiles to mainland Japanese patients, with frequent alterations in TCR/NF‐ĸB (eg, PRKCB, PLCG1, and CARD11) and T‐cell trafficking pathways (CCR4 and CCR7), in contrast with North American patients who exhibited a predominance of epigenome‐associated gene mutations. Some mutations, especially GATA3 and RHOA, were detected more frequently in Okinawan patients than in mainland Japanese patients. Compared to HTLV‐1‐taxB, HTLV‐1‐taxA was significantly dominant in Okinawan patients with these mutations (GATA3, 34.1% vs 14.6%, P = .044; RHOA, 24.4% vs 6.3%, P = .032), suggesting the contribution of viral strains to these mutation frequencies. From a clinical viewpoint, we identified a significant negative impact of biallelic inactivation of PRDM1 (P = .027) in addition to the previously reported PRKCB mutations, indicating the importance of integrated genetic analysis. This study suggests that heterogeneous genetic abnormalities in ATLL depend on the viral strain as well as on the ethnic background. This warrants the need to develop therapeutic interventions considering regional characteristics.
Targeted next‐generation sequencing and single nucleotide polymorphism array were applied to analyze aggressive adult T‐cell leukemia/lymphoma in Okinawa, which were not included in prior genomic studies. Our results showed that HTLV‐1 tax subgroup‐A was associated with high alteration frequencies in GATA3 and RHOA. Clinically, biallelic alterations, not heterozygous deletions or mutations, of PRDM1 were significantly associated with poor prognosis.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d517e8449311ef95a6ecc2bd5d2502d6Test
http://europepmc.org/articles/PMC7935801Test

المؤلفون: Elena Anghileri, Junfei Zhao, Valeria Cuccarini, Gaetano Finocchiaro, Monica Patanè, Natalia Di Ianni, Marica Eoli, Tiziana Langella, Antonio Iavarone, Serena Pellegatta, Raul Rabadan, Bianca Pollo, Rosina Paterra

المصدر: Cancer Immunology, Immunotherapy. 70:831-842

مصطلحات موضوعية: Adult, Cancer Research, Biopsy, T-Lymphocytes, T cell, Programmed Cell Death 1 Receptor, Immunology, Neuroimaging, Germline, 03 medical and health sciences, 0302 clinical medicine, Immunophenotyping, Immune system, Exome Sequencing, Biomarkers, Tumor, Humans, Immunology and Allergy, Medicine, Molecular Targeted Therapy, Immune Checkpoint Inhibitors, Temozolomide, business.industry, medicine.disease, Colorectal Neoplasms, Hereditary Nonpolyposis, Combined Modality Therapy, Immunohistochemistry, Magnetic Resonance Imaging, Lynch syndrome, Treatment Outcome, medicine.anatomical_structure, Oncology, MSH2, Mutation, Retreatment, Cancer research, Female, Neoplasm Recurrence, Local, Nivolumab, Glioblastoma, business, 030215 immunology, medicine.drug

الوصف: Glioblastomas (GBMs) in patients harboring somatic or germinal mutations of mismatch-repair (MMR) genes exhibit a hypermutable phenotype. Here, we describe a GBM patient with increased tumor mutational burden and germline MMR mutations, treated using anti-PD1 therapy. A woman with newly diagnosed GBM (nGBM) was treated by surgery, radiotherapy, and temozolomide. The tumor recurred after 13 months leading to a second surgery and treatment with nivolumab. Whole-exome sequencing was performed on the nGBM, recurrent GBM (rGBM), and blood. Immune infiltration was investigated by immunohistochemistry and the immune response in the blood during treatment was analyzed by flow cytometry. High density of infiltrating CD163 + cells was found in both GBM specimens. Large numbers of CD3 + and CD8 + T cells were homogeneously distributed in the nGBM. The infiltration of CD4 + T cells and a different CD8 + T cell density were observed in the rGBM. Both GBM shared 12,431 somatic mutations, with 113 substitutions specific to the nGBM and 1,683 specific to the rGBM. Germline variants included pathogenic mutation in the MSH2 (R359S) gene, suggesting the diagnosis of Lynch syndrome. Systemic immunophenotyping revealed the generation of CD8 + T memory cells and persistent activation of CD4 + T cells. The patient is still receiving nivolumab 68 months after the second surgery. Our observations indicate that the hypermutator phenotype associated with germinal mutations of MMR genes and abundant T-cell infiltration contributes to a durable clinical benefit sustained by a persistent and robust immune response during anti-PD1 therapy.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::91e9d6d866c397beb05c63097c4dbcb1Test
https://doi.org/10.1007/s00262-020-02769-4Test

المؤلفون: Charles Lance Cowey, Emilie Scherrer, April Beeks, Clemens Krepler, Marley Boyd, Kathleen M. Aguilar

المصدر: Cancer Medicine, Vol 9, Iss 21, Pp 7863-7878 (2020)
Cancer Medicine

مصطلحات موضوعية: 0301 basic medicine, Oncology, Male, Cancer Research, Skin Neoplasms, Time Factors, Programmed Cell Death 1 Receptor, Medical Oncology, immunology, 0302 clinical medicine, Risk Factors, Medicine, Community Health Services, Molecular Targeted Therapy, Immune Checkpoint Inhibitors, Melanoma, Original Research, Community based, Aged, 80 and over, Middle Aged, MAP Kinase Kinase Kinases, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Progression-Free Survival, 030220 oncology & carcinogenesis, Female, Drug Utilization, Adult, Proto-Oncogene Proteins B-raf, medicine.medical_specialty, First line, Risk Assessment, survival, lcsh:RC254-282, 03 medical and health sciences, Internal medicine, Humans, Radiology, Nuclear Medicine and imaging, Protein Kinase Inhibitors, Advanced melanoma, Aged, Retrospective Studies, Adult patients, business.industry, target therapy, Clinical Cancer Research, biomarkers, Retrospective cohort study, 030104 developmental biology, Propensity score matching, Mutation, Observational study, business

الوصف: Introduction Anti‐PD‐1 monotherapies (aPD‐1) and BRAF/MEK inhibitors (BRAF/MEKi) changed the BRAF‐mutant advanced melanoma treatment landscape. This study aimed to improve the understanding of real‐world treatment patterns and optimal treatment sequence. Methods This was a retrospective study of BRAF‐mutant advanced melanoma patients who initiated 1L aPD‐1 or BRAF/MEKi in the US Oncology Network between 1 January 2014 and 31 December 2017, followed through 31 December 2018. Patient and treatment characteristics were assessed descriptively, with Kaplan‐Meier methods used for time‐to‐event endpoints. As the primary analysis, overall survival (OS) and physician‐assessed progression‐free survival (rwPFS) were evaluated with Cox proportional hazard regression models and propensity score matching (n = 49). Results A total of 224 patients were included (median age 61 years, 62.9% male, 89.7% white): 36.2% received aPD‐1 and 63.8% BRAF/MEKi. Median OS and rwPFS were longer among aPD‐1 vs BRAF/MEKi patients (OS: not reached vs 13.9 months, log‐rank P = .0169; rwPFS: 7.6 vs 6.5 months, log‐rank P = .0144). Receipt of aPD‐1 was associated with improved OS (HR = 0.602 vs BRAF/MEKi [95%CI 0.382‐0.949]; P = .0287). Among patients without an event within 6 months of 1L initiation, receipt of aPD‐1 was associated with a decreased risk of progression or death from 6 months onwards (HR = 0.228 [95%CI 0.106‐0.493]; P = .0002). This association was not observed among patients within 6 months of 1L initiation (HR = 1.146; 95% CI 0.755‐1.738). Results from the propensity score‐matched pairs were consistent with these trends. Conclusion These results suggest a clinical benefit of 1L aPD‐1 compared to BRAF/MEKi after 6 months of treatment for BRAF‐mutant advanced melanoma. Future research should explore factors associated with early progression and their relationship with clinical outcomes.
While both aPD‐1 and BRAF/MEKi are approved for BRAF‐mutant advanced melanoma, limited evidence exists comparing these therapies, particularly to understand the optimal treatment sequence. This study provides evidence of a clinical benefit of first‐line (1L) aPD‐1 compared to BRAF/MEKi after 6 months among patients with BRAF‐mutant advanced melanoma who received care in a large network of US community oncology clinics.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::96fc6bc46c16e1f918585ef9a89a846dTest
https://doaj.org/article/ee976dd75d584d12914c8df2bc5510e8Test

المؤلفون: Huanhuan Yin, Cuihua Feng, Yujie Tan, Xiangling Sun, Wei Guo, Ruili Li

المصدر: Journal of Immunology Research, Vol 2020 (2020)
Journal of Immunology Research

مصطلحات موضوعية: Adult, Cytotoxicity, Immunologic, Oncology, medicine.medical_specialty, Multivariate analysis, Article Subject, Combination therapy, Programmed Cell Death 1 Receptor, Immunology, Uterine Cervical Neoplasms, Kaplan-Meier Estimate, B7-H1 Antigen, Immunophenotyping, 03 medical and health sciences, Lymphocytes, Tumor-Infiltrating, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Tumor, medicine, Overall survival, Humans, Immunology and Allergy, In patient, Molecular Targeted Therapy, Anti pd1, Immune Checkpoint Inhibitors, Objective response, Metastatic cervical cancer, Aged, business.industry, General Medicine, Middle Aged, RC581-607, Prognosis, Magnetic Resonance Imaging, Treatment Outcome, 030220 oncology & carcinogenesis, Cytokines, Female, Immunologic diseases. Allergy, Tomography, X-Ray Computed, business, Research Article, 030215 immunology

الوصف: Background. We investigated the efficacy of TILs and anti-PD1 combination therapy in patients with metastatic cervical cancer with low MSI expression and PDL1-negative. Methods. A total of 80 patients were put on TILs and anti-PD1 combination therapy, and the progression-free survival time (PFS) and overall survival time (OS) were assessed by Kaplan–Meier analysis. Univariate and multivariate analyses were performed to identify factors that could predict the prognosis of metastatic cervical cancer in the previously described patients. Results. The objective response rate was 25%, whereas the mPFS and mOS were 6.1 and 11.3 months, respectively. The therapeutic efficacy was influenced by the characteristics of TILs, infection with HPV, and development of fever just after the therapy. Conclusion. Overall, our results show that the combination therapy of TILs and anti-PD1 significantly improves the prognosis of metastatic cervical cancer.

وصف الملف: text/xhtml

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::721b2d90497b5fff7641c5df3560f9cdTest
https://doi.org/10.1155/2020/8345235Test