Characterization of Effusion-Infiltrating T Cells

Abstract

Purpose: While naïve T cells circulate between peripheral blood and lymph nodes, memory effector T cells acquire certain surface molecules that enable them to travel to peripheral tissues and exert their effector function. We analyzed whether deficient numbers of effector-type T cells within the malignant effusion might contribute to tumor escape from immunosurveillance.Experimental Design: We analyzed the expression of a broad range of adhesion molecules and chemokine receptors (CD62L, CD56, CCR4, CCR5, CCR7, CXCR3, CLA, and integrin ␣4␤7) on tumor-associated lymphocytes in effusions and peripheral blood lymphocytes of patients with malignant ascites (n ‫؍‬ 11) or malignant pleural effusion (n ‫؍‬ 16). A tumor-associated lymphocyte:peripheral blood lymphocyte ratio was calculated as an indicator for homing of lymphocytes into the effusions and was compared with patients with nonmalignant ascites (n ‫؍‬ 17).Results: Patients with malignancies show an increased enrichment of T cells expressing the phenotype of "naïve" (CD62L؉ and CD45RA؉CCR7؉), "central memory" (CD45RA-CCR7؉), and type 2-polarized (CCR4؉) T cells within their effusions. In contrast, enrichment of "effector"-type (CD45RA-CCR7؊ or CD45RA؉CCR7؊) and presumably type 1-polarized T cells (CCR5؉) at the tumor site is deficient. The same is true for natural killer cells and potentially cytotoxic CD56؉ T cells.Conclusions: Here we show for the first time that patients with malignant effusions show a deficient enrichment of T cells expressing the phenotype of type-1-polarized effector T cells at the tumor site. This mechanism is likely to contribute to the escape of tumor cells from immunosurveillance.

Targeting miR-23a in CD8+ cytotoxic T lymphocytes prevents tumor-dependent immunosuppression

“…In these patients, pleural effusion CTLs are a good reflection of TILs, as they have received similar conditioning in the tumor microenvironment (e.g., by IL-10 and TGF-β; ref. 68) and are known to be functionally reminiscent of TILs (69,70). As a control for basal gene expression outside the tumor and to normalize for interindividual variations, we also isolated CTLs obtained from the peripheral blood (PBMCs) of each patient for paired-sample analysis.…”

Altered CD94/NKG2A and perforin expression reduce the cytotoxic activity in malignant pleural effusions

“…In this regard, it has been previously demonstrated that patients with malignant effusions show a deficient enrichment of T cells expressing the phenotype of type-1-polarised effector T cells at the tumour site. 8 Although, CD8+ CTL and NK cell recovered from cancer PF have a reduced expression of the inhibitory receptor CD94/ NKG2A, they exhibit a reduced cytotoxic activity against cancer cells when compared to CD8+ CTL and NK cells recovered from autologous PB. NKG2A receptor deficiency may contribute to this reduced cytotoxic activity by two mechanisms: (1) high concentrations of IFN-c increase the levels of HLA-E which activate the receptor thus promoting its internalisation (being the receptor no longer on the surface) 11 ; (2) the lack of the NKG2A receptor enhances regulatory functions with an advantage for the tumour cell.…”

“…6 The CD94/NKG2A heterodimer is an inhibitory receptor expressed by CD8+ CTL and NK cells that, upon activation by HLA-E, downregulates their cytolytic activity against tumour cells. 7 Although, some studies have shown that pleural effusion mononuclear cells exhibit several functional defects, 8 limited information is available regarding the expression and the activity of the CD94/NKG2A complex in CD8+ CTL and NK cells isolated from malignant pleural effusions.…”

Tumor Necrosis Factor-α Promotes Malignant Pleural Effusion

“…In addition, several lines of evidence support the notion that tumor cells produce mediators that sculpt the tumor microenvironment in favor of sustained growth and metastasis (9,10,16,17). Human MPE contains inflammatory cells and mediators (1,3,18), but their role in disease progression is uncertain (19)(20)(21).…”