Abstract A51: Identification of cytokine network signaling abnormalities in immune cells from cancer patients.
Authors: Miyahira Andrea K. , Simons Diana L. , Dirbas Frederick , Guardino Ellie , Sheth Shruti , Carlson Robert , Lee Peter P. 
Published: August 2014

Abstract
The innate and adaptive immune systems have the capacity to recognize and eliminate transformed cells while the ability of tumors to evade and abrogate immune functions appears to be a requisite for disease progression. Abnormalities in essentially every immune population have been documented in cancer patients and murine tumor models. Thus, the immune system is a crucial target for cancer therapeutics in order to achieve a true cure.
The cytokine JAK-STAT signaling network is a key instrument of immune system communication and directs a multitude of immune functions. Because of the integral role in regulation of immune functions as well as the intricate crosstalk that occurs within cytokine signaling networks, alterations in these networks in cancer patients are likely to be key contributing factors in immune dysfunction.
We have previously shown that IFNα and IFNγ signaling are impaired in lymphocytes from breast cancer, melanoma, and gastrointestinal cancer patients. In this study we sought to determine whether additional cytokine signaling pathways are altered in immune cells from cancer patients. Phospho-flow cytometry was used to measure STAT phosphorylation in response to 10 cytokines from the IFN, gp130, γC, and the IL3 cytokine families, to provide a broad picture of the global cytokine network in peripheral blood immune cells. Included in this analysis were patient cohorts with various carcinomas including breast, lung, gastrointestinal, and melanoma, as well as patients with psoriasis, an epidermal hyperplasia resulting from chronic inflammatory cytokine production by persistently activated immune cells.
Preliminary analysis of our study has revealed that compared with healthy controls, cancer and psoriasis patients exhibit altered responses to multiple additional cytokines in various immune cell subsets. We hypothesize that chronic inflammation which occurs in the settings of both cancer and psoriasis contributes to cytokine signaling defects and are exploring the mechanisms and the functional consequences of these defects on T cell function.
Understanding how alterations in cytokine responsiveness contribute to immune dysfunction will enable correction of these signaling defects to restore anti-tumor immune function and enhance the ability of the host immune response to control cancer.
This work was supported by the U.S. Army Medical Research and Materiel Command under W81XWH-10-1-0616 and W81XWH-06-1-0417, NIH Molecular and Cellular Immunobiology Training Grant No. 5 T32 AI07290-24, and NIH R01 CA130817.
Citation Format: Andrea K. Miyahira, Diana L. Simons, Frederick Dirbas, Ellie Guardino, Shruti Sheth, Robert Carlson, Peter P. Lee. Identification of cytokine network signaling abnormalities in immune cells from cancer patients. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr A51.