B Cells versus T Cells in the Tumor Microenvironment of Malignant Lymphomas. Are the Lymphocytes Playing the Roles of Muhammad Ali versus George Foreman in Zaire 1974?

Publisher's version (útgefin grein)Malignant lymphomas are a heterogeneous group of malignancies that develop both in nodal and extranodal sites. The different tissues involved and the highly variable clinicopathological characteristics are linked to the association between the lymphoid neoplastic cells and the tissues they infiltrate. The immune system has developed mechanisms to protect the normal tissue from malignant growth. In this review, we aim to explain how T lymphocyte-driven control is linked to tumor development and describe the tumor-suppressive components of the resistant framework. This manuscript brings forward a new insight with regard to intercellular and intracellular signaling, the immune microenvironment, the impact of therapy, and its predictive implications. A better understanding of the key components of the lymphoma environment is important to properly assess the role of both B and T lymphocytes, as well as their interplay, just as two legendary boxers face each other in a heavyweight title final, as was the case of Ali versus Foreman.The research on the lymphoma microenvironment was funded by an internal grant of the Iuliu Hatieganu University, School of Doctoral Studies (PCD 2018-2021) (Minodora Desmirean), under the frame of European Social Found, Human Capital Operational Program 2014-2020, project no. POCU/380/6/13/125171 (Minodora Desmirean) and the Romanian Ministry of Research and Innovation, CCCDI-UEFISCDI, Project No. PN-III-P4-ID-PCCF-2016-0112 within PNCDI III, by an award for Young Research Teams 2020-2022 (Grant No. PN-III-P1-1.1-TE-2019-0271) (both Ciprian Tomuleasa) as well as by an international collaborative grant of the European Economic Space between Romania and Iceland 2020-2022 (Grant No. 19-COP-0031) (Ciprian Tomuleasa)."Peer Reviewed

B Cells versus T Cells in the Tumor Microenvironment of Malignant Lymphomas. Are the Lymphocytes Playing the Roles of Muhammad Ali versus George Foreman in Zaire 1974?

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadMalignant lymphomas are a heterogeneous group of malignancies that develop both in nodal and extranodal sites. The different tissues involved and the highly variable clinicopathological characteristics are linked to the association between the lymphoid neoplastic cells and the tissues they infiltrate. The immune system has developed mechanisms to protect the normal tissue from malignant growth. In this review, we aim to explain how T lymphocyte-driven control is linked to tumor development and describe the tumor-suppressive components of the resistant framework. This manuscript brings forward a new insight with regard to intercellular and intracellular signaling, the immune microenvironment, the impact of therapy, and its predictive implications. A better understanding of the key components of the lymphoma environment is important to properly assess the role of both B and T lymphocytes, as well as their interplay, just as two legendary boxers face each other in a heavyweight title final, as was the case of Ali versus Foreman. Keywords: B lymphocytes; T lymphocytes; lymphocyte inter-talk; malignant lymphomas; tumor microenvironment.Iuliu Hatieganu University, School of Doctoral Studies RomanianMinistry of Research and Innovation, CCCDI-UEFISCDI within PNCDI III European Economic Spac

A narrative review of central nervous system involvement in acute leukemias.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadAcute leukemias (both myeloid and lymphoblastic) are a group of diseases for which each year more successful therapies are implemented. However, in a subset of cases the overall survival (OS) is still exceptionally low due to the infiltration of leukemic cells in the central nervous system (CNS) and the subsequent formation of brain tumors. The CNS involvement is more common in acute lymphocytic leukemia (ALL), than in adult acute myeloid leukemia (AML), although the rates for the second case might be underestimated. The main reasons for CNS invasion are related to the expression of specific adhesion molecules (VLA-4, ICAM-1, VCAM, L-selectin, PECAM-1, CD18, LFA-1, CD58, CD44, CXCL12) by a subpopulation of leukemic cells, called "sticky cells" which have the ability to interact and adhere to endothelial cells. Moreover, the microenvironment becomes hypoxic and together with secretion of VEGF-A by ALL or AML cells the permeability of vasculature in the bone marrow increases, coupled with the disruption of blood brain barrier. There is a single subpopulation of leukemia cells, called leukemia stem cells (LSCs) that is able to resist in the new microenvironment due to its high adaptability. The LCSs enter into the arachnoid, migrate, and intensively proliferate in cerebrospinal fluid (CSF) and consequently infiltrate perivascular spaces and brain parenchyma. Moreover, the CNS is an immune privileged site that also protects leukemic cells from chemotherapy. CD56/NCAM is the most important surface molecule often overexpressed by leukemic stem cells that offers them the ability to infiltrate in the CNS. Although asymptomatic or with unspecific symptoms, CNS leukemia should be assessed in both AML/ALL patients, through a combination of flow cytometry and cytological analysis of CSF. Intrathecal therapy (ITT) is a preventive measure for CNS involvement in AML and ALL, still much research is needed in finding the appropriate target that would dramatically lower CNS involvement in acute leukemia. Keywords: Acute leukemias; central nervous system involvement (CNS involvement); clinical management; pathophysiology.Iuliu Hatieganu University-School of Doctoral Studies (PCD 2019-2021) Romanian Government Ion Chiricuta Oncology Institute Cluj Napoca European Economic Spac

C-reactive protein as robust laboratory value associated with prognosis in patients with stage III non-small cell lung cancer (NSCLC) treated with definitive radiochemotherapy

Abstract To evaluate the prognostic value of biomarkers from peripheral blood obtained as routine laboratory assessment for overall survival in a cohort of stage III non-small cell lung cancer (NSCLC) patients treated with definitive radiochemotherapy at a high-volume cancer center. Seven blood biomarkers from 160 patients treated with definitive radiochemotherapy for stage III NSCLC were analyzed throughout the course treatment. Parameters were preselected using univariable and multivariable proportional hazards analysis and were assessed for internal validity using leave-one-out cross validation. Cross validated classifiers including biomarkers in addition to important clinical parameters were compared with classifiers containing the clinical parameters alone. An increased C-reactive protein (CRP) value in the final week of radiotherapy was found as a prognostic factor for overall survival, both as a continuous (HR 1.099 (1.038–1.164), p < 0.0012) as well as categorical variable splitting data at the median value of 1.2 mg/dl (HR 2.214 (1.388–3.531), p < 0.0008). In the multivariable analysis, the CRP value-maintained significance with an HR of 1.105 (1.040–1.173) and p-value of 0.0012. The cross validated classifier using CRP at the end of radiotherapy in addition to clinical parameters separated equally sized high and low risk groups more distinctly than a classifier containing the clinical parameters alone (HR = 2.786 (95% CI 1.686–4.605) vs. HR = 2.287 (95% CI 1.407–3.718)). Thus, the CRP value at the end of radiation therapy has successfully passed the crucial cross-validation test. The presented data on CRP levels suggests that inflammatory markers may become increasingly important during definitive radiochemotherapy, particularly with the growing utilization of immunotherapy as a consolidation therapy for stage III NSCLC