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Making cold malignant pleural effusions hot: driving novel immunotherapies.

ABSTRACT: Malignant pleural effusions, arising from either primary mesotheliomas or secondary malignancies, heralds advanced disease and poor prognosis. Current treatments, including therapeutic thoracentesis and tube thoracostomy, are largely palliative. The immunosuppressive environment within the pleural cavity includes myeloid derived suppressor cells, T-regulatory cells, and dysfunctional T cells. The advent of effective immunotherapy with checkpoint inhibitors and adoptive cell therapies for lung cancer and other malignancies suggests a renewed examination of local and systemic therapies for this malady. Prior strategies reporting remarkable success, including instillation of the cytokine interleukin-2, perhaps coupled with checkpoint inhibitors, should be further evaluated in the modern era.

SUBMITTER: Murthy P

PROVIDER: S-EPMC6422374 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Making cold malignant pleural effusions hot: driving novel immunotherapies.

Murthy Pranav P Ekeke Chigozirim N CN Russell Kira L KL Butler Samuel C SC Wang Yue Y Luketich James D JD Soloff Adam C AC Dhupar Rajeev R Lotze Michael T MT

Oncoimmunology 20190122 4

Malignant pleural effusions, arising from either primary mesotheliomas or secondary malignancies, heralds advanced disease and poor prognosis. Current treatments, including therapeutic thoracentesis and tube thoracostomy, are largely palliative. The immunosuppressive environment within the pleural cavity includes myeloid derived suppressor cells, T-regulatory cells, and dysfunctional T cells. The advent of effective immunotherapy with checkpoint inhibitors and adoptive cell therapies for lung ca ...[more]

PMID: 30906651

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Project description:IntroductionPleural effusions frequently signal disseminated cancer. Diagnostic markers of pleural malignancy at presentation that would assess cancer risk and would streamline diagnostic decisions remain unidentified.MethodsA consecutive cohort of 323 patients with pleural effusion (PE) from different etiologies were recruited between 2013 and 2017 and was retrospectively analyzed. Data included history, chest X-ray, and blood/pleural fluid cell counts and biochemistry. Group comparison, receiver-operator characteristics, unsupervised hierarchical clustering, binary logistic regression, and random forests were used to develop the malignant pleural effusion detection (MAPED) score. MAPED was validated in an independent retrospective UK cohort (n = 238).ResultsFive variables showed significant diagnostic power and were incorporated into the 5-point MAPED score. Age > 55 years, effusion size > 50% of the most affected lung field, pleural neutrophil count 〈 2,500/mm3, effusion protein 〉 3.5 g/dL, and effusion lactate dehydrogenase > 250 U/L, each scoring one point, predicted underlying cancer with the area under curve(AUC) = 0.819 (P < 10-15) in the derivation cohort. The integrated discrimination improvement of MAPED scores showed an increase compared to cytology (p <0.001). Decision curve analysis indicated that the MAPED score generated net clinical benefit. In the validation dataset, the AUC of MAPED scores was 0.723 ( P = 3 × 10-9) for the MAPED score. Interestingly, MAPED correctly identified 33/42(79%) of cytology-negative patients that indeed had cancer.ConclusionsThe MAPED score identifies malignant pleural effusions with satisfactory accuracy and can be used complementary to cytology to streamline diagnostic procedures.Condensed abstractDiagnostic markers for malignant pleural effusions remain uncertain. The MAPED score identifies malignant pleural effusions and complements cytology and confers no additional risk to the patient or cost to the healthcare system.

Dataset Information

Making cold malignant pleural effusions hot: driving novel immunotherapies.

Publications

Making cold malignant pleural effusions hot: driving novel immunotherapies.

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