Dataset Information

Mesothelin-specific Immune Responses Predict Survival of Patients With Brain Metastasis.

ABSTRACT:

Background

Patients with advanced malignancies, e.g. lung cancer, ovarian cancer or melanoma, frequently present with brain metastases. Clinical presentation and disease progression of cancer is in part shaped by the interaction of the immune system with malignant cells. Antigen-targeted immune responses have been implicated in the prolonged survival of patients with cancer. This includes the tumor-associated antigen (TAA) mature mesothelin, a 40kDa cell surface-bound antigen that is overexpressed in several malignancies including lung ovarian and pancreatic cancer. We examined in an observational, prospective study the survival of patients with brain metastases in association with clinical parameters and cellular immune responses to molecularly defined TAAs or viral (control) target antigens.

Methods

Immune cells in peripheral blood obtained from thirty-six patients with brain metastases were tested for cytokine production in response to a broad panel of defined viral and TAA target antigens, including full-length mesothelin. Incubation of immune cells with antigenic targets was carried out in i) medium alone, (ii) in a cytokine cocktail of interleukin (IL)-2/IL-15/IL-21, or (iii) IL-2/IL-7. Supernatants were tested for interferon gamma (IFN-?) production, after which univariate and multivariate analyses (Cox stepwise regression model) were performed to identify independent clinical and immunological factors associated with patient survival. Patients were followed-up for at least 500days after surgery or until death.

Findings

Univariate analysis identified age, gender, radiotherapy and mutational load as clinical parameters affecting survival of patients with brain metastases. Cox multivariate analysis showed that radiotherapy (P=0·004), age (P=0·029) and IFN-? responses to mature mesothelin, conditioned by IL-2/IL-7 (P=0·045) were independent predictors of the survival of patients from surgery up to follow-up or death.

Interpretation

This is the first evidence that immune responses to mesothelin serve as a marker of increased overall survival in patients with brain metastases, regardless of the primary tumor origin. Analyses of immunological markers could potentially serve as prognostic markers in patients with brain metastases and help to select patients in need for adjunct, immunological, treatment strategies.

SUBMITTER: Zhenjiang L

PROVIDER: S-EPMC5605370 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Publications

Mesothelin-specific Immune Responses Predict Survival of Patients With Brain Metastasis.

Zhenjiang Liu L Rao Martin M Luo Xiaohua X Sandberg Elisabeth E Bartek Jiri J Schoutrop Esther E von Landenberg Anna A Meng Qingda Q Valentini Davide D Poiret Thomas T Sinclair Georges G Peredo Inti-Harvey IH Dodoo Ernest E Maeurer Markus M

EBioMedicine 20170830

<h4>Background</h4>Patients with advanced malignancies, e.g. lung cancer, ovarian cancer or melanoma, frequently present with brain metastases. Clinical presentation and disease progression of cancer is in part shaped by the interaction of the immune system with malignant cells. Antigen-targeted immune responses have been implicated in the prolonged survival of patients with cancer. This includes the tumor-associated antigen (TAA) mature mesothelin, a 40kDa cell surface-bound antigen that is ove ...[more]

PMID: 28888924

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Dataset Information

Mesothelin-specific Immune Responses Predict Survival of Patients With Brain Metastasis.

Background

Methods

Findings

Interpretation

Publications

Mesothelin-specific Immune Responses Predict Survival of Patients With Brain Metastasis.

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