The Experts below are selected from a list of 34569 Experts worldwide ranked by ideXlab platform
Perttu Koskenvesa - One of the best experts on this subject based on the ideXlab platform.
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immune cell contexture in the Bone Marrow Tumor microenvironment impacts therapy response in cml
Leukemia, 2018Co-Authors: Oscar Bruck, Sami Blom, Olli Dufva, Riku Turkki, Himanshu Chheda, Antonio Ribeiro, Panu E Kovanen, Tero Aittokallio, Perttu KoskenvesaAbstract:Increasing evidence suggests that the immune system affects prognosis of chronic myeloid leukemia (CML), but the detailed immunological composition of the leukemia Bone Marrow (BM) microenvironment is unknown. We aimed to characterize the immune landscape of the CML BM and predict the current treatment goal of tyrosine kinase inhibitor (TKI) therapy, molecular remission 4.0 (MR4.0). Using multiplex immunohistochemistry (mIHC) and automated image analysis, we studied BM tissues of CML patients (n = 56) and controls (n = 14) with a total of 30 immunophenotype markers essential in cancer immunology. CML patients’ CD4+ and CD8+ T-cells expressed higher levels of putative exhaustion markers PD1, TIM3, and CTLA4 when compared to control. PD1 expression was higher in BM compared to paired peripheral blood (PB) samples, and decreased during TKI therapy. By combining clinical parameters and immune profiles, low CD4+ T-cell proportion, high proportion of PD1+TIM3−CD8+ T cells, and high PB neutrophil count were most predictive of lower MR4.0 likelihood. Low CD4+ T-cell proportion and high PB neutrophil counts predicted MR4.0 also in a validation cohort (n = 52) analyzed with flow cytometry. In summary, the CML BM is characterized by immune suppression and immune biomarkers predicted MR4.0, thus warranting further testing of immunomodulatory drugs in CML treatment.
Tero Aittokallio - One of the best experts on this subject based on the ideXlab platform.
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immune cell contexture in the Bone Marrow Tumor microenvironment impacts therapy response in cml
Leukemia, 2018Co-Authors: Oscar Bruck, Sami Blom, Olli Dufva, Riku Turkki, Himanshu Chheda, Antonio Ribeiro, Panu E Kovanen, Tero Aittokallio, Perttu KoskenvesaAbstract:Increasing evidence suggests that the immune system affects prognosis of chronic myeloid leukemia (CML), but the detailed immunological composition of the leukemia Bone Marrow (BM) microenvironment is unknown. We aimed to characterize the immune landscape of the CML BM and predict the current treatment goal of tyrosine kinase inhibitor (TKI) therapy, molecular remission 4.0 (MR4.0). Using multiplex immunohistochemistry (mIHC) and automated image analysis, we studied BM tissues of CML patients (n = 56) and controls (n = 14) with a total of 30 immunophenotype markers essential in cancer immunology. CML patients’ CD4+ and CD8+ T-cells expressed higher levels of putative exhaustion markers PD1, TIM3, and CTLA4 when compared to control. PD1 expression was higher in BM compared to paired peripheral blood (PB) samples, and decreased during TKI therapy. By combining clinical parameters and immune profiles, low CD4+ T-cell proportion, high proportion of PD1+TIM3−CD8+ T cells, and high PB neutrophil count were most predictive of lower MR4.0 likelihood. Low CD4+ T-cell proportion and high PB neutrophil counts predicted MR4.0 also in a validation cohort (n = 52) analyzed with flow cytometry. In summary, the CML BM is characterized by immune suppression and immune biomarkers predicted MR4.0, thus warranting further testing of immunomodulatory drugs in CML treatment.
Oscar Bruck - One of the best experts on this subject based on the ideXlab platform.
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immune cell contexture in the Bone Marrow Tumor microenvironment impacts therapy response in cml
Leukemia, 2018Co-Authors: Oscar Bruck, Sami Blom, Olli Dufva, Riku Turkki, Himanshu Chheda, Antonio Ribeiro, Panu E Kovanen, Tero Aittokallio, Perttu KoskenvesaAbstract:Increasing evidence suggests that the immune system affects prognosis of chronic myeloid leukemia (CML), but the detailed immunological composition of the leukemia Bone Marrow (BM) microenvironment is unknown. We aimed to characterize the immune landscape of the CML BM and predict the current treatment goal of tyrosine kinase inhibitor (TKI) therapy, molecular remission 4.0 (MR4.0). Using multiplex immunohistochemistry (mIHC) and automated image analysis, we studied BM tissues of CML patients (n = 56) and controls (n = 14) with a total of 30 immunophenotype markers essential in cancer immunology. CML patients’ CD4+ and CD8+ T-cells expressed higher levels of putative exhaustion markers PD1, TIM3, and CTLA4 when compared to control. PD1 expression was higher in BM compared to paired peripheral blood (PB) samples, and decreased during TKI therapy. By combining clinical parameters and immune profiles, low CD4+ T-cell proportion, high proportion of PD1+TIM3−CD8+ T cells, and high PB neutrophil count were most predictive of lower MR4.0 likelihood. Low CD4+ T-cell proportion and high PB neutrophil counts predicted MR4.0 also in a validation cohort (n = 52) analyzed with flow cytometry. In summary, the CML BM is characterized by immune suppression and immune biomarkers predicted MR4.0, thus warranting further testing of immunomodulatory drugs in CML treatment.
Kara Olson - One of the best experts on this subject based on the ideXlab platform.
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t cells from the Tumor microenvironment of patients with progressive myeloma can generate strong Tumor specific cytolytic responses to autologous Tumor loaded dendritic cells
Proceedings of the National Academy of Sciences of the United States of America, 2002Co-Authors: Madhav V Dhodapkar, Joseph Krasovsky, Kara OlsonAbstract:Most untreated cancer patients develop progressive Tumors. We tested the capacity of T lymphocytes from patients with clinically progressive, multiple myeloma to develop killer function against fresh autologous Tumor. In this malignancy, it is feasible to reproducibly evaluate freshly isolated Tumor cells and T cells from the Marrow Tumor environment. When we did this with seven consecutive patients, with all clinical stages of disease, we did not detect reactivity to autologous cancer cells. However, both cytolytic and IFN-γ-producing responses to autologous myeloma were generated in six of seven patients after stimulation ex vivo with dendritic cells that had processed autologous Tumor cells. The antiTumor effectors recognized fresh autologous Tumor but not nonTumor cells in the Bone Marrow, myeloma cell lines, dendritic cells loaded with Tumor-derived Ig, or allogeneic Tumor. Importantly, these CD8+ effectors developed with similar efficiency by using T cells from both the blood and the Bone Marrow Tumor environment. Therefore, even in the setting of clinical Tumor progression, the Tumor bed of myeloma patients contains T cells that can be activated readily by dendritic cells to kill primary autologous Tumor.
Nicholas J Szerlip - One of the best experts on this subject based on the ideXlab platform.
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dural cells release factors which promote cancer cell malignancy and induce immunosuppressive markers in Bone Marrow myeloid cells
Neurosurgery, 2018Co-Authors: Nicholas J Szerlip, Alexandra Calinescu, Eleanor C Smith, Rebecca Tagett, Katrina L Clines, Henry H Moon, Russell S Taichman, Catherine Van Poznak, Gregory A ClinesAbstract:Background Thirty per cent of cancer patients develop spine metastases with a substantial number leading to spinal cord compression and neurological deficits. Many demonstrate a propensity toward metastasis to the posterior third of the vertebral body. The dura, the outer layer of the meninges, lies in intimate contact with the posterior border of the vertebral body and has been shown to influence adjacent Bone. The effects of the dura on Bone Marrow and cancer cells have not been examined. Understanding the biology of spinal metastasis will provide insights into mechanisms of cancer growth and allow for new treatment strategies. Objective To examine the extent to which dura influences Bone Marrow/Tumor cell metastatic characteristics. Methods Dura conditioned media (DCM) from primary dura was examined for the ability to stimulate Tumor cell proliferation/invasion and to alter Bone Marrow cell populations. RNA sequencing of dural fibroblasts was performed to examine expression of cytokines and growth factors. Results DCM induced a significant increase in invasion and proliferation of multiple Tumor cell lines, and of patient-derived primary spinal metastatic cells. DCM also increased the proliferation of Bone Marrow myeloid cells, inducing expression of immunosuppressive markers. RNA sequencing of dural fibroblasts demonstrated abundant expression of cytokines and growth factors involved in cancer/immune pathways. Conclusion Factors released by primary dural cells induce proliferation of Tumor cells and alter Bone Marrow to create a fertile environment for Tumor growth. The dura therefore may play an important role in the increased incidence of metastases to adjacent Bone.