Peripheral CD8+ T cell proliferation is prognostic for patients with advanced thoracic malignancies

Abstract

There is a complex interplay between the immune system and a developing tumor that is manifest in the way that the balance of T cell subsets in the local tumor environment reflects clinical outcome. Tumor infiltration by CD8(+) T cells and regulatory T cells (Treg) is associated with improved and reduced survival, respectively, in many cancer types. However, little is known of the prognostic value of immunological parameters measured in peripheral blood. In this study, peripheral CD8(+) T cells and Treg from 43 patients with malignant mesothelioma or advanced non-small-cell lung cancer scheduled to commence palliative chemotherapy were assessed by flow cytometry and evaluated for association with patient survival. Patients had a higher proportion of peripheral Treg, proliferating CD8(+) T cells and CD8(+) T cells with an activated effector phenotype compared with age-matched healthy controls. Higher proportions of Treg and proliferating CD8(+) T cells were both associated with poor survival in univariate analyses (hazard ratio [HR] 3.81, 95 % CI 1.69-8.57; p < 0.01 and HR 2.86, 95 % CI 1.26-6.50; p < 0.05, respectively). CD8(+) T cell proliferation was independently predictive of reduced survival in multivariate analysis (HR 2.58, 95 % CI 1.01-6.61; p < 0.05). These findings suggest that peripheral CD8(+) T cell proliferation can be a useful prognostic marker in patients with thoracic malignancies planned for palliative chemotherapy.

Serial immunomonitoring of cancer patients receiving combined antagonistic anti-CD40 and chemotherapy reveals consistent and cyclical modulation of T cell and dendritic cell parameters

“…5b). We also examined “effector” CD38 hi HLA-DR hi CD8+ T cells, which are activated in an antigen-specific manner as previously reported from studies of chronic viral infection, and are present at elevated levels in cancers including mesothelioma compared with healthy controls [18–22]. These cells are predominantly proliferating, and exhibit low expression of Bcl-2 (an anti-apoptotic protein downregulated following antigen-specific T cell activation) [19, 23].…”

“…The effects of cisplatin/pemetrexed are well known, particularly with respect to depletion of proliferating and activated cells as can be observed from our lymphocyte data, and may well alter the immunological background of patients in a manner that can affect the subsequent dose of anti-CD40. We have previously demonstrated a profound reduction in the proportion of Ki67+ CD8+, CD4+ and Treg as well as activated effector CD8+ T cells on day 8 after chemotherapy, which recovers to baseline prior to the next chemotherapy cycle [18]. Thirdly, the effects of the agonistic anti-CD40 antibody, administered on Day 8.…”

Predictive value of peripheral regulatory T cells in non-small cell lung cancer patients undergoing radiotherapy

“…However, the predictive roles of lymphocyte subpopulations in peripheral blood were not well studied. McCoy et al [19] found that an elevated proportion of peripheral Treg cells was associated with poor survival in patients with thoracic malignancies. A very recent study has demonstrated that the prognostic value of CD4+ Treg subtypes in NSCLC patients received chemotherapy [20].…”

Stimulating immune responses to fight cancer: Basic biology and mechanisms

“…For example, in NSCLC, increased dendritic, 42 CD4, CD8+, 43,44 macrophages, 45,46 and NK cells 47 suggest a favorable prognosis. On the other hand, increased levels of T-reg 44,48 cells suggest a less favorable prognosis.…”