Ratio of Immune Response to Tumor Burden Predicts Survival Via Regulating Functions of Lymphocytes and Monocytes in Diffuse Large B-Cell Lymphoma

Abstract

Background/Aims: Diffuse large B-cell lymphoma (DLBCL) is an aggressive disease, and is the most common type of lymphoma in adults. Although significant progress in treatment has been made using chemotherapy combinations, there exist a large amount of relapse or refractory cases. Thus, effective clinical biomarkers for DLBCL are urgently needed. Our study aims to explore the predictive significance of using the immune response to tumor burden ratio [defined as the lymphocyte to monocyte ratio (LMR)/lactate dehydrogenase (LDH) levels] in 184 DLBCL patients and the potential mechanism underlying the use of the LMR to tumor burden ratio in predicting patient survival. Methods: The correlation between serum LDH levels and tumor levels assessed by PET-CT was determined using Spearman’s correlation analysis. Clinical data from 184 DLBCL patients was assessed using receiver operating characteristic curve analysis and survival analysis. The potential correlation between tumor burden and lymphocytes or monocytes was analyzed by immunohistochemical staining, flow cytometry, and ELISA analysis of patient samples. In addition, we performed in vitro studies to further determine the effects of tumor burden on the anti-tumor activity of T lymphocytes. Results: We observed that serum LDH was an excellent surrogate marker of tumor burden in DLBCL patients, and that the ratio of LMR to LDH was an independent prognostic biomarker capable of predicting survival in DLBCL patients. Further analysis showed that a high tumor burden was correlated with decreased Ki67 expression in T cells, either in the solid tumor tissue or in the circulating blood. In addition, based on an in vitro co-culture study, a higher tumor burden led to the suppression of the anti-tumor response of T cells. Furthermore, we found that a higher tumor burden was correlated with the differentiation of monocytes to tumor associated macrophages in the tumor micro-environment. Both results demonstrate the importance of considering both the immune system and tumor burden for prognostic analysis. Conclusion: Our study has identified a novel clinical biomarker, namely, the immune response to tumor burden ratio, that can be used to distinguish survival outcomes in DLBCL patients, and demonstrated the potential mechanism underlying the use of this biomarker, that incorporates both the immune system and tumor burden, for use in future clinical applications.

Plasma fibrinogen level as possible prognostic biomarker in diffuse large B-cell lymphoma

“…Serum LDH was demonstrated by Ji et al [20] as a perfect surrogate marker of tumour burden in DLBCL patients. Therefore, the positive correlation between baseline fibrinogen and LDH levels in our study might suggest a possible connection between fibrinogen level and tumour burden.…”

Systemic immune response associated with radiation therapy in B‑cell non‑Hodgkin's lymphoma of Waldeyer's ring

“…To the best of our knowledge, this is the first study to estimate the prognostic value of the LMR in RT-treated patients with WR-B-NHL and investigate the potential application of the LMR combined with RT on the systemic immune response, as well as the combination of RT with immunotherapies. Accumulating studies have demonstrated that survival outcomes in patients with lymphoma are associated with systemic inflammation (22)(23)(24)(30)(31)(32). The peripheral inflammatory cells, including lymphocytes and monocytes, represent significant markers of systematic inflammatory response (20)(21)(22)(23).…”

“…Therefore, the LMR may be a better biomarker to evaluate the immune activities of the host. As reported, the LMR may reflect the degree of systemic immunity and is regarded as an important prognostic indicator in a variety of malignancies, including B-NHL (22)(23)(24). There are several studies focusing on the role of the LMR on therapeutic responsiveness of chemotherapy regimens (30,37); however, few studies have compared the LMR with clinical response to RT (38), which is also an important therapeutic modality to treat patients with WR-B-NHL.…”

“…Clinically, surrogate markers based on systemic immunity, such as, peripheral blood parameters, including the absolute lymphocyte count (ALC), absolute monocyte count (AMC), lymphocyte to monocyte ratio (LMR), neutrophil to lymphocyte ratio (NLR), are considered immunologically relevant, and have been reported to aid in the prognostic evaluation of various types of malignancies (19)(20)(21)(22)(23)(24). To date, it remains unclear which immune marker predicts clinical outcomes of RT and is associated with RT affecting systemic immunity in patients with WR-B-NHL.…”

Rasio Neutrofil Limfosit sebagai Prediktor Neutropenia Akut Awitan Pertama Pascakemoterapi R-CHOP pada Pasien Diffuse Large B-cell Lymphoma

“…30 Limfosit mempunyai efek anti-tumor yang penting dalam imunitas tubuh. 33 Dengan tingginya kadar limfosit, maka sistem imunitas tubuh semakin kuat sehingga risiko neutropenia pascakemoterapi akan lebih rendah. Aktivasi limfosit T merupakan langkah utama pada keadaan respons imun yang efektif.…”