Secretome of pleural effusions associated with non-small cell lung cancer (NSCLC) and malignant mesothelioma: therapeutic implications

The cover for issue 60 of Oncotarget features Figure 3, "Comparison of cytokine levels grouped by function," by Donnenberg, et al.

Cryopreserved cell-free PE fluid from 101 NSCLC patients, 8 mesothelioma and 13 with benign PE was assayed for a panel of 40 cytokines/chemokines using the Luminex system.

Comparing NSCLC PE and published plasma levels of CAR-T recipients, both were dominated by sIL-6R and IL-6 but NSCLC PE had more VEGF, FGF2 and TNF, and less IL-2, IL-4, IL-13, IL-15, MIP1 and IFN.

A dampened effector response was detected in NSCLC PE, but not mesothelioma or benign PE.

Figure 3: Comparison of cytokine levels grouped by function. Cytokine concentrations were standardized such that the geometric mean control value in the benign PE group was 0 with a standard deviation of 1 and grouped by function (Table 1).

Dr. Albert D. Donnenberg and Dr. Vera S. Donnenberg said, "The pleura represent a common site of metastasis for non-small cell lung cancer (NSCLC) and are the primary site of tumorigenesis in malignant mesothelioma."

These conditions are accompanied by the development of pleural effusions, accumulations of serous fluid rich in tumor cells, mesothelial cells, immune cells, as well as the cytokines and chemokines which they secrete.

In this report the authors compare levels of 40 cytokines and chemokines in non-small cell lung cancer, mesothelioma and benign pleural effusions, with the goal of identifying druggable targets and interventions that can change the pleural environment from one that suppresses immunity and promotes tumor invasiveness, to one conducive to anti-tumor effector responses.

The Donnenberg/Donnenberg Research Team concluded that despite this hostile environment, there is evidence in NSCLC PE of a nascent immune effector response that may be harnessed therapeutically by modifying the local pleural immune environment with antibody-based therapeutics, by ex vivo activation and reinstillation of pleural T cells or engineered T cells.

The authors go on to speculate that conditioning the immune environment of the pleura will greatly increase the chances of success.

Full text - https://doi.org/10.18632/oncotarget.27290

Correspondence to - Albert D. Donnenberg - [email protected] and Vera S. Donnenberg - [email protected]

Keywords - pleural effusion, non-small cell lung cancer, malignant mesothelioma, cytokines, IL-6