Immune Characteristics of Chinese Diffuse Large B-Cell Lymphoma Patients: Implications for Cancer Immunotherapies

Abstract

Immunotherapeutic agents have demonstrated encouraging signs of clinical utility in non-Hodgkin lymphoma. The goal of this study is to analyze the immune characteristics of Chinese patients with diffuse large B-cell lymphoma (DLBCL) to inform the development of immunotherapies in this patient population. Tumor samples from 211 DLBCL patients were analyzed for cell of origin (COO) and immune characteristics using the NanoString platform as well as MYC protein expression through immunohistochemistry. Lower incidence of the germinal center B-cell (GCB) subtype (93/211, 44.1%) was observed in this cohort. Compared to the GCB subtype, the activated B-cell (ABC) subtype was associated with significantly increased expression of multiple pro-inflammatory gene signatures and decreased expression of anti-inflammatory gene signatures. Instead of affecting the pro-inflammatory genes, MYC protein overexpression showed a negative correlation with the expression of T-cell receptor (TCR) and T regulatory genes as well as the OX40 gene. Regardless of COO, higher PD-L1 or IDO1 gene expression correlated with increased expression of T effector and Interferon-γ gene signatures while the expression of multiple oncogenes including ACTR3B, ERBB2, AKT2 and SMARCD1 was down-regulated. Our findings may thus be helpful in guiding further development of immunotherapies for the different subsets of Chinese DLBCL patients.

OX40 and OX40L protein expression of tumor infiltrating lymphocytes in non-small cell lung cancer and its role in clinical outcome and relationships with other immune biomarkers

“…To our knowledge, it is the first research to analyze the role of OX40/OX40L in early-stage resectable NSCLC and demonstrate its relationships with PD-1/PD-L1, TILs and patients' clinical outcomes. OX40/OX40L has already been studied previously as an immune characteristic biomarker in some other cancer types, including lymphoma, hepatocellular carcinoma, Leukemia, ovarian, neuroblastoma, head and neck squamous cell carcinoma, gastric cancer and breast cancer (52)(53)(54)(55)(56)(57)(58)(59)(60)(61)(62)(63). The TILs OX40 was reported to correlate with patient survival.…”

Spontaneously reversible adrenal nodules in primary diffuse large B-cell testicular lymphoma mimicking an extranodal involvement: A case report

“…After the exclusion of the main organic and functional causes of adrenal hypertrophy, the most likely possibility is that of stress-related hypertrophy whereby stress resulted in a disturbance of organic homeostasis, due to lymphomatous proliferation. In this regard, we recall the natural immunosuppressive and anti-inflammatory function of corticosteroids produced by the adrenal gland, and the recent scientific evidence of a pro-inflammatory state created by DLBCL [18] . Vincent et al.…”

“…already demonstrated in 1994, a statistically significant correlation between adrenal hyperplasia and the presence of neoplasia, both carcinomatous and lymphomatous, suggesting the activation of the HPA axis by hormone-like bioactive factors secreted by lymphomatous / tumor cells as the cause[19]. It has been demonstrated that DLBCL lymphomas may induce the activation of pro-inflammatory genes, creating a pro-inflammatory microenvironment favorable to lymphomatous proliferation [18] . In conclusion, adrenal hyperplasia may be a paraneoplastic condition, and the concept of stress should be evaluated as organic and biochemical changes [19] .…”

Impact of MYC on Anti-Tumor Immune Responses in Aggressive B Cell Non-Hodgkin Lymphomas: Consequences for Cancer Immunotherapy

“…Furthermore, two other cohorts of de novo and relapsed DLBCL patients reported a negative correlation between MYC and PD-L1 [ 63 , 64 ]. Finally, some other studies were not able to detect any correlation between MYC and PD-L1 at all in either DLBCL cell lines [ 80 ], nor in DLBCL patients [ 60 , 66 , 68 , 81 ]. Notably, EBV infection causes B cells to escape from immune surveillance [ 82 , 83 ] partly by PD-L1 overexpression [ 84 , 85 ], adding further complexity to the relationship between MYC and PD-L1 in EBV-associated DLBCL and BL.…”

“…The immunoglobulin superfamily member CD80 binds to co-costimulatory molecules from the CD28/B7 family on T cells [ 59 ]. However, in a cohort of 211 de novo DLBCL patients MYC protein overexpression did not correlate with CD40 gene expression, but an association was shown with decreased levels of the co-stimulatory immune checkpoint OX40 ( TNFRSF4 ) gene, decreased T cell receptor signaling molecules and regulatory T cell gene FOXP3 [ 60 ].…”