Tumour-infiltrating CD4+ and CD8+ lymphocytes as predictors of clinical outcome in glioma

Abstract

Background:T lymphocyte infiltration has been detected in glioma, although its significance remains unclear. The purpose of the present study was to explore the prognostic value of CD4+ and CD8+ tumour-infiltrating lymphocytes (TILs) in glioma, and the prognostic value of infiltrating Forkhead box protein 3 (FoxP3+) regulatory T cells were also investigated.Methods:CD4+, FoxP3+ and CD8+ TILs were assessed by immunohistochemical staining of tissue microarray cores from 284 gliomas. Kaplan–Meier analysis and Cox proportional hazards models were used to examine the survival function of these TILs in 90 glioblastoma patients.Results:The number of CD8+ TILs was inversely correlated with tumour grade (P=0.025), whereas the number of CD4+ TILs was positively correlated with tumour grade (P=0.002). FoxP3+ TILs were only observed in glioblastomas, but not in low-grade astrocytomas or oligodendroglial tumours. Among patients with glioblastoma, none of CD4+ TILs, FoxP3+ TILs and CD8+ TILs alone was significantly associated with patient prognosis. However, the presence of high CD4+ and low CD8+ TIL levels was an independent predictor of poor progress-free survival (multivariate hazard ratio (HR) 1.618, 95% confidence interval (CI) 1.245–2.101, P<0.001) and poor overall survival (multivariate HR 1.508, 95% CI 1.162–1.956, P=0.002). Moreover, pseudoprogression was more often found in patients with high CD4+ TILs and high CD8+ TILs.Conclusions:The combination of CD4+ and CD8+ TILs is a predictor of clinical outcome in glioblastoma patients, and a high level of CD4+ TILs combined with low CD8+ TILs was associated with unfavourable prognosis.

Targeting Neoantigens in Glioblastoma

“…[26][27][28][29][30] Together, these data support the notion that both the humoral and cellular arms of the immune system are able to be primed against GBM antigens. However, it remains unclear by which mechanism these adaptive immune responses are generated; which antigens they recognize; the functional capacity of such naturally occurring responses; and the role these spontaneous immune responses play in driving immune escape.…”

Cord blood T cells mediate enhanced antitumor effects compared with adult peripheral blood T cells

“…murine models and also in cancer patients, including those with leukemia. [30][31][32][33][34][35][36][37][38][39][40] In a murine model of allogeneic bone marrow transplantation for acute T-cell leukemia 39 and chronic myeloid leukemia, 40 infusion of mixed donor CD4 balance toward Th1 in the CB TILs is noteworthy, because this occurred despite the fact that naïve CB CD4 1 T cells are reported to be physiologically biased toward Th2, produce lower levels of IFN-g than adult naïve T cells in vitro, and are hypermethylated at cytosine guanine dinucleotide and non-cytosine guanine dinucleotide sites within the IFN-g promoter. 4 This therefore suggests that CB CD4 We therefore plan to optimize disruption of CCR7 receptor in the CB T cells using the CRISPR/Cas9 system to more closely define the role of CCR7 receptor in tumor homing.…”

Can lateral ventricle contact predict the ontogeny and prognosis of glioblastoma?

“…Pre-and post-operative contrast-enhanced MRI images were available for all the patients. Molecular information (including MGMT promoter methylation and IDH1 mutation status) and mRNA microarray data were available for the 43 glioblastomas from Chinese Glioma Genome Atlas (CGGA; http:// www.cgcg.org.cn) as previously described [3,11]. Surgical resections were performed between January 2007 and December 2009 by neurosurgeons who used similar techniques in each patient.…”

“…As such, the identification of clinical and molecular markers that predict disease outcome is needed in order to tailor treatment regimens to individual patients [3]. Moreover, the ontogeny of glioblastomas-which has important therapeutic implications-is still largely unknown.…”