Antigens, CD/analysis ; Antigens, Differentiation, Myelomonocytic/analysis ; Biopsy ; Bone Marrow/immunology* ; Bone Marrow/pathology ; Bone Marrow Examination ; CD3 Complex/analysis ; CD8-Positive T-Lymphocytes/immunology* ; CD8-Positive T-Lymphocytes/pathology ; Chemotaxis, Leukocyte* ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lymphocyte Count ; Lymphoma, Large B-Cell, Diffuse/immunology* ; Lymphoma, Large B-Cell, Diffuse/mortality ; Lymphoma, Large B-Cell, Diffuse/pathology ; Lymphoma, Large B-Cell, Diffuse/therapy ; Macrophages/immunology ; Macrophages/pathology ; Male ; Middle Aged ; Neoplasm Staging ; Predictive Value of Tests ; Proportional Hazards Models ; Receptors, Cell Surface/analysis ; Time Factors ; Tumor Microenvironment
Keywords
Bone marrow ; CD8+ T cells ; Diffuse large B-cell lymphoma ; Microenvironment ; Prognosis
Abstract
The implications of infiltrating immune cells, especially T cells and macrophages, in the bone marrow (BM) microenvironment of patients with diffuse large B-cell lymphoma (DLBCL) have rarely been studied. We aimed to investigate the significance of infiltrating immune cells in the BM microenvironment as a prognostic factor for DLBCL patients. Using the initial pretreatment BM biopsy obtained from 198 DLBCL patients, we semiquantitatively evaluated CD3+ T cells, CD8+ T cells, and CD163+ macrophages that infiltrate into the paratrabecular and interstitial areas of BM by immunohistochemistry and analyzed their clinicopathological and prognostic implications. Levels of infiltrating CD3+ T cells, CD8+ T cells, and CD163+ macrophages were significantly higher in BM with DLBCL involvement (BMI-positive group) than in that without DLBCL involvement (BMI-negative group). Infiltration of CD8+ T cells significantly increased in cases with advanced Ann Arbor stage, elevated lactate dehydrogenase level, extranodal site involvement ≥2 sites, higher Eastern Cooperative Oncology Group performance status, and higher International Prognostic Index (IPI) risk. High levels of CD3+ T cells were significantly associated with age ≤60, and high levels of CD163+ macrophages were associated with advanced Ann Arbor stage and higher IPI risk. High infiltration of CD8+ T cells was significantly related to inferior overall and recurrence-free survival rate, even in the BMI-negative group. High infiltration of CD8+ T cells within the pretreatment BM was related to poor prognosis, and might be a useful prognostic factor of DLBCL patients. Therefore, evaluation of CD8+ T cells is helpful for predicting prognosis in initial pretreatment BM biopsy of DLBCL patients.