Flow cytometry quantification of tumor-infiltrating lymphocytes to predict the survival of patients with diffuse large B-cell lymphoma


<jats:sec><jats:title>Introduction</jats:title><jats:p>Our previous studies have demonstrated that tumor-infiltrating lymphocytes (TILs), including normal B cells, T cells, and natural killer (NK) cells, in diffuse large B-cell lymphoma (DLBCL) have a significantly favorable impact on the clinical outcomes of patients treated with standard chemoimmunotherapy. In this study, to gain a full overview of the tumor immune microenvironment (TIME), we assembled a flow cytometry cohort of 102 patients diagnosed with DLBCL at the Duke University Medical Center.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We collected diagnostic flow cytometry data, including the proportion of T cells, abnormal B cells, normal B cells, plasma cells, NK cells, monocytes, and granulocytes in fresh biopsy tissues at clinical presentation, and analyzed the correlations with patient survival and between different cell populations.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>We found that low T cell percentages in all viable cells and low ratios of T cells to abnormal B cells correlated with significantly poorer survival, whereas higher percentages of normal B cells among total B cells (or high ratios of normal B cells to abnormal B cells) and high percentages of NK cells among all viable cells correlated with significantly better survival in patients with DLBCL. After excluding a small number of patients with low T cell percentages, the normal B cell percentage among all B cells, but not T cell percentage among all cells, continued to show a remarkable prognostic effect. Data showed significant positive correlations between T cells and normal B cells, and between granulocytes and monocytes. Furthermore, we constructed a prognostic model based on clinical and flow cytometry factors, which divided the DLBCL cohort into two equal groups with remarkable differences in patient survival and treatment response.</jats:p></jats:sec><jats:sec><jats:title>Summary</jats:title><jats:p>TILs, including normal B cells, T cells, and NK cells, are associated with favorable clinical outcomes in DLBCL, and flow cytometry capable of quantifying the TIME may have additional clinical utility for prognostication.</jats:p></jats:sec>






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Publication Info

Yu, Tiantian, Zijun Y Xu-Monette, Anand Lagoo, Wen Shuai, Bangchen Wang, Jadee Neff, Luis F Carrillo, Eric D Carlsen, et al. (n.d.). Flow cytometry quantification of tumor-infiltrating lymphocytes to predict the survival of patients with diffuse large B-cell lymphoma. Frontiers in Immunology, 15. 10.3389/fimmu.2024.1335689 Retrieved from https://hdl.handle.net/10161/29899.

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Zijun Yidan Xu-Monette

Assistant Professor in Pathology

My research efforts have been focused on identifying prognostic and therapeutic biomarkers in B-cell lymphoma. My research interests also include investigation of molecular and immune mechanisms underlying the poor clinical outcomes of lymphoma, the pathogenesis and evolution of drug resistant clones, and development of novel therapies for aggressive B-cell lymphoma.


Anand Shreeram Lagoo

Professor of Pathology

My clinical interests are focused on diagnosis of hematological malignancies (leukemia, lymphoma, Hodgkin disease, multiple myeloma, etc). I devote majority of my effort to provide diagnostic interpretation based on morphological examination of blood, bone marrow, lymph node, other lymphoid organs like spleen, as well as any other organ and tissue suspected to harbor lymphoma or leukemia.  The morphological findings are integrated with results of ancillary studies including flow cytometry, cytogenetics and molecular diagnostics, as well as key clinical, radiographic, and laboratory findings. 
As medical director of the Clinical Flow Cytometry laboratory, I oversee the operations of the lab to ensure accuracy and timely delivery of these high complexity diagnostic tests.  Development and validation of flow cytometric tests to provide prognostic information and evaluation of therapeutic targets to guide treatment is also an important aspect of my work.  
My translational research interests include-
1. Correlation of flow cytometric, cytogenetic and molecular findings in acute myeloid leukemias with myelodysplasia associated changes and in acute leukemias with monocytic differentiation.
2. Morphological changes following non-conventional treatments for myeloid, lymphoid, and plasma cell neoplasms.
3. The spectrum of lymphoid tissue involvement by plasmacytic / plasmacytoid cells.


Jadee Lee Neff

Assistant Professor of Pathology

As a diagnostic hematopathologist and molecular genetic pathologist, my clinical interests are focused on the histologic examination of tissue and bone marrow biopsies to diagnose hematologic malignancies (leukemia, lymphoma, myeloma, etc.) as well as testing DNA from tumors or from blood to detect inherited or acquired mutations that can guide therapeutic management and predict clinical outcome.  My research interests involve 1) understanding the biology of T-cell and NK-cell neoplasms; 2) defining the immunomodulatory response to neoplastic disease; 3) developing methods to monitor immune response and thereby refine tumor immunotherapy; and 4) exploring novel applications of tumor genetics in the diagnosis, prognosis, and management of cancer.


Luis Felipe Carrillo

Assistant Professor of Pathology

My academic interests include flow cytometry, myeloid neoplasms, lymphoma diagnosis, cutaneous lymphomas, and Epstein Barr virus. In addition to my clinical duties, I have a strong interest in medical education, which includes teaching medical students, residents, and fellows.


Eric D. Carlsen

Assistant Professor of Pathology

I'm a hematopathologist with interest in cutaneous and small B-cell lymphomas, molecular methods for diagnosis and prognostication of myeloid and lymphoid neoplasms, minimal residual disease modalities, infectious hematopathology, medical and GME trainee education, and emerging technology and automation in laboratory hematology.  I serve as a CLIA director for several clinical laboratories on DUH's campus, including our specialty laboratories performing clinical electrophoresis and bone marrow biopsy processing.  I also serve as the Program Director for Duke's Hematopathology Fellowship.


Sergio Pina-Oviedo

Associate Professor of Pathology

My research interests include hematolymphoid tumors, thoracic and lung pathology, mediastinal lymphomas, correlation between morphology and molecular alterations of tumors, infectious diseases, and the history of pathology.

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