EBV oncogene N-LMP1 induces CD4 T cell-mediated angiogenic blockade in the murine tumor model.

Antivascular immunity may provide long-term protection by preventing neovascularization that precedes tumor progression. Although the tumorigenesis promoted by EBV-encoded oncogene latent membrane protein 1 derived from Taiwanese nasopharyngeal carcinoma (N-LMP1) has been demonstrated, the potential of N-LMP1 for inducing immune surveillance remains elusive. In this article, we describe the immunogenicity of N-LMP1 (1510) and its induction of antivascular immunity in a transplantable tumor model in immunocompetent BALB/c mice. The immunogenicity of N-LMP1 was evaluated on the basis of tumor rejection following immunization. The impact of the immunization on the dynamics of tumor angiogenesis was assessed by temporal noninvasive dynamic contrast-enhanced magnetic resonance imaging and was further confirmed by histologic study and vascular count. Through the experiments of in vivo depletion and adoptive transfer, CD4 T cells were identified as effectors that depend on IFN-γ for tumor prevention. The response was further verified by the identification of an MHC H-2 I-E(d)-restricted peptide derived from N-LMP1 and by the immunization of mice with N-LMP1 peptide-loaded dendritic cells. These studies provide insight into N-LMP1-specific immunity in vivo, which suggests that CD4 T cells may play an important role in angiogenic surveillance against LMP1-associated cancer via tumor stroma targeting.

Clinical study of DA-EPOCH regimen combined with or without rituximab in treatment of young newly diagnosed patients with middle and high-risk diffuse large B-cell lymphoma / 白血病·淋巴瘤

Objective@#To observe the clinical efficacy and prognosis of DA-EPOCH regimen combined with or without rituximab [(R)-DA-EPOCH regimen] in treatment of young newly diagnosed patients with middle and high-risk diffuse large B-cell lymphoma (DLBCL).@*Methods@#The clinical data of 107 young newly diagnosed middle to high-risk DLBCL patients treated with (R)-DA-EPOCH regimen at Guizhou Cancer Hospital between November 2014 and December 2018 were retrospectively analyzed. The efficacies were analyzed by grouping according to rituximab (65 cases in R-DA-EPOCH group and 42 cases in DA-EPOCH group), and according to involved-filed radiotherapy (IFRT) after chemotherapy (99 cases with chemotherapy indications including 59 cases with IFRT and 40 cases without IFRT).@*Results@#The objective response rate (ORR) was 86.0% (92/107). The 1-, 2-year overall survival (OS) rate was 90.6% and 75.3%. The 1-, 2-year progression-free survival (PFS) rate was 79.1% and 56.5%. The ORR, 1-year OS rate, 2-year OS rate, 1-year PFS rate and 2-year PFS rate in R-DA-EPOCH group were higher than those in DA-EPOCH group [87.7% (57/65) vs. 83.3% (35/42), 94.8% vs. 84.9%, 80.4% vs. 68.2%, 90.5% vs. 77.0%, 61.0% vs. 50.8%, respectively), but there were no statistical differences (all P > 0.05). The ORR of IFRT group and non-IFRT group was 98.2% (56/57) and 80.0% (32/40) (χ 2 = 7.225, P = 0.007). The 2-year OS rate was 86.0% and 63.3% (P < 0.05). Main adverse reactions caused by radiotherapy were local skin mucosa reactions of grade Ⅰ-Ⅱ [42.4% (25/59)]. Multivariate analysis showed that albumin value after treatment was an independent prognosis factor affecting OS rate (95% CI 2.709-21.433, P < 0.01). Gender (95% CI 0.020-0.318, P < 0.01), albumin level (95% CI 2.097-12.219, P < 0.01), Beta 2 microglobulin level (95% CI 0.080-0.602, P < 0.01) and absolute lymphocyte count/absolute monocyte count (95% CI 0.113-0.720, P < 0.01) after treatment were independent prognosis factors affecting PFS rate.@*Conclusions@#The young newly diagnosed patients with middle and high-risk DLBCL are highly heterogeneous. Rituximab combined with DA-EPOCH regimen can improve the efficacy of patients. IFRT after chemotherapy may increase the short-term efficacy and OS, and the adverse reactions are tolerant.