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The effect of lung cancer on cytokine expression in peripheral blood mononuclear cells.

Chang DH, Rutledge JR, Patel AA, Heerdt BG, Augenlicht LH, Korst RJ - PLoS ONE (2013)

Bottom Line: PBMC gene expression of CCL3, IL8 and IL1β was higher in lung cancer patients compared to the same patients at each of four sequential timepoints after removal of their tumors, while CXCL10 and IL2Rα were essentially unchanged.When non-cancer patients underwent surgery for benign diseases, these cytokine expression changes were not demonstrable.We conclude that PBMCs from stage I lung cancer patients possess distinct cytokine expression patterns compared to both non-cancer patients, and lung cancer patients following tumor removal.

View Article: PubMed Central - PubMed

Affiliation: Center for Cancer Research and Genomic Medicine, The Daniel and Gloria Blumenthal Cancer Center, Paramus, New Jersey, United States of America.

ABSTRACT
The purpose of this study is to evaluate cytokine expression by peripheral blood mononuclear cells (PBMC) from stage I lung cancer patients and to confirm these expression patterns by exposing PBMCs to lung cancer cells in vitro. Five altered cytokines in stage I lung cancer patients (CCL3, IL8, IL1β, CXCL10, sIL2Rα) were identified in plasma from subjects (n = 15) before and after resection using a 30-plex panel protein assay. Gene expression studies using quantitative RT-qPCR were performed on PBMCs from stage I lung cancer patients (n = 62) before and after resection, and compared to non-cancer patients (n = 32) before and after surgery for benign disease. Co-culture experiments that exposed healthy donor PBMCs to lung cancer cells in vitro were performed to evaluate the effect on PBMC cytokine expression. PBMC gene expression of CCL3, IL8 and IL1β was higher in lung cancer patients compared to the same patients at each of four sequential timepoints after removal of their tumors, while CXCL10 and IL2Rα were essentially unchanged. This pattern was also detected when lung cancer patients were compared to non-cancer patients. When non-cancer patients underwent surgery for benign diseases, these cytokine expression changes were not demonstrable. Lung cancer cell lines, but not benign bronchial epithelial cells, induced similar changes in cytokine gene and protein expression by healthy donor PBMCs in an in vitro co-culture system. We conclude that PBMCs from stage I lung cancer patients possess distinct cytokine expression patterns compared to both non-cancer patients, and lung cancer patients following tumor removal. These expression patterns are replicated by healthy donor PBMCs exposed to lung cancer cell lines, but not benign bronchial epithelial cells in vitro. These findings have implications for understanding the immune response to lung cancer.

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Gene expression of 5 selected cytokines in lung cancer patients compared to non-cancer patients.A. Preoperative PBMC gene expression in stage I lung cancer patients (n = 62) compared to non-cancer patients scheduled to undergo thoracic surgery for benign disease (n = 32). CCL3: p = 0.003; IL8: p = 0.23; IL1β: p = 0.05; CXCL10: p = 0.55; IL2Rα: p = 0.01. B. Three month postoperative PBMC gene expression in stage I lung cancer patients (n = 48) compared to non-cancer patients (n = 11). CCL3: p = 0.79; IL8: p = 0.3; IL1β: p = 0.1; CXCL10: p = 0.8; IL2Rα: p = 0.29. C. Twelve month postoperative PBMC gene expression in stage I lung cancer patients (n = 40) compared to non-cancer patients (n = 7). CCL3: p = 0.76; IL8: p = 0.52; IL1β: p = 0.87; CXCL10: p = 0.22; IL2Rα: p = 0.58. For all panels, each bar represents the ratio of the mean expression level in the cancer patients over the mean expression level in the control patients, expressed in log2 scale. A positive value indicates that expression is higher in the cancer patients compared to the control patients. Two sample t-tests were used to determine the significance of the differences in expression.
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pone-0064456-g003: Gene expression of 5 selected cytokines in lung cancer patients compared to non-cancer patients.A. Preoperative PBMC gene expression in stage I lung cancer patients (n = 62) compared to non-cancer patients scheduled to undergo thoracic surgery for benign disease (n = 32). CCL3: p = 0.003; IL8: p = 0.23; IL1β: p = 0.05; CXCL10: p = 0.55; IL2Rα: p = 0.01. B. Three month postoperative PBMC gene expression in stage I lung cancer patients (n = 48) compared to non-cancer patients (n = 11). CCL3: p = 0.79; IL8: p = 0.3; IL1β: p = 0.1; CXCL10: p = 0.8; IL2Rα: p = 0.29. C. Twelve month postoperative PBMC gene expression in stage I lung cancer patients (n = 40) compared to non-cancer patients (n = 7). CCL3: p = 0.76; IL8: p = 0.52; IL1β: p = 0.87; CXCL10: p = 0.22; IL2Rα: p = 0.58. For all panels, each bar represents the ratio of the mean expression level in the cancer patients over the mean expression level in the control patients, expressed in log2 scale. A positive value indicates that expression is higher in the cancer patients compared to the control patients. Two sample t-tests were used to determine the significance of the differences in expression.

Mentions: To determine if PBMCs from stage I lung cancer patients have higher expression levels of CCL3, IL8 and IL1β than patients without lung cancer, the RT-qPCR results from the preoperative PBMC samples from the stage I lung cancer (n = 62) and control cohorts (n = 32) were compared. As shown in Figure 3, the mean expression in lung cancer patients was significantly higher relative to controls for CCL3 and IL1β (10 and 29 fold, respectively). Although not statistically significant, mean expression of IL8 was 6 fold higher in the lung cancer patients relative to controls. In contrast, although statistically significant, IL2Rα expression was only 2 fold higher in the lung cancer patients, while CXCL10 expression was essentially unchanged. Importantly, at three and twelve months after surgery, expression levels appear to equalize between the cancer and control cohorts (Figure 3).


The effect of lung cancer on cytokine expression in peripheral blood mononuclear cells.

Chang DH, Rutledge JR, Patel AA, Heerdt BG, Augenlicht LH, Korst RJ - PLoS ONE (2013)

Gene expression of 5 selected cytokines in lung cancer patients compared to non-cancer patients.A. Preoperative PBMC gene expression in stage I lung cancer patients (n = 62) compared to non-cancer patients scheduled to undergo thoracic surgery for benign disease (n = 32). CCL3: p = 0.003; IL8: p = 0.23; IL1β: p = 0.05; CXCL10: p = 0.55; IL2Rα: p = 0.01. B. Three month postoperative PBMC gene expression in stage I lung cancer patients (n = 48) compared to non-cancer patients (n = 11). CCL3: p = 0.79; IL8: p = 0.3; IL1β: p = 0.1; CXCL10: p = 0.8; IL2Rα: p = 0.29. C. Twelve month postoperative PBMC gene expression in stage I lung cancer patients (n = 40) compared to non-cancer patients (n = 7). CCL3: p = 0.76; IL8: p = 0.52; IL1β: p = 0.87; CXCL10: p = 0.22; IL2Rα: p = 0.58. For all panels, each bar represents the ratio of the mean expression level in the cancer patients over the mean expression level in the control patients, expressed in log2 scale. A positive value indicates that expression is higher in the cancer patients compared to the control patients. Two sample t-tests were used to determine the significance of the differences in expression.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3675097&req=5

pone-0064456-g003: Gene expression of 5 selected cytokines in lung cancer patients compared to non-cancer patients.A. Preoperative PBMC gene expression in stage I lung cancer patients (n = 62) compared to non-cancer patients scheduled to undergo thoracic surgery for benign disease (n = 32). CCL3: p = 0.003; IL8: p = 0.23; IL1β: p = 0.05; CXCL10: p = 0.55; IL2Rα: p = 0.01. B. Three month postoperative PBMC gene expression in stage I lung cancer patients (n = 48) compared to non-cancer patients (n = 11). CCL3: p = 0.79; IL8: p = 0.3; IL1β: p = 0.1; CXCL10: p = 0.8; IL2Rα: p = 0.29. C. Twelve month postoperative PBMC gene expression in stage I lung cancer patients (n = 40) compared to non-cancer patients (n = 7). CCL3: p = 0.76; IL8: p = 0.52; IL1β: p = 0.87; CXCL10: p = 0.22; IL2Rα: p = 0.58. For all panels, each bar represents the ratio of the mean expression level in the cancer patients over the mean expression level in the control patients, expressed in log2 scale. A positive value indicates that expression is higher in the cancer patients compared to the control patients. Two sample t-tests were used to determine the significance of the differences in expression.
Mentions: To determine if PBMCs from stage I lung cancer patients have higher expression levels of CCL3, IL8 and IL1β than patients without lung cancer, the RT-qPCR results from the preoperative PBMC samples from the stage I lung cancer (n = 62) and control cohorts (n = 32) were compared. As shown in Figure 3, the mean expression in lung cancer patients was significantly higher relative to controls for CCL3 and IL1β (10 and 29 fold, respectively). Although not statistically significant, mean expression of IL8 was 6 fold higher in the lung cancer patients relative to controls. In contrast, although statistically significant, IL2Rα expression was only 2 fold higher in the lung cancer patients, while CXCL10 expression was essentially unchanged. Importantly, at three and twelve months after surgery, expression levels appear to equalize between the cancer and control cohorts (Figure 3).

Bottom Line: PBMC gene expression of CCL3, IL8 and IL1β was higher in lung cancer patients compared to the same patients at each of four sequential timepoints after removal of their tumors, while CXCL10 and IL2Rα were essentially unchanged.When non-cancer patients underwent surgery for benign diseases, these cytokine expression changes were not demonstrable.We conclude that PBMCs from stage I lung cancer patients possess distinct cytokine expression patterns compared to both non-cancer patients, and lung cancer patients following tumor removal.

View Article: PubMed Central - PubMed

Affiliation: Center for Cancer Research and Genomic Medicine, The Daniel and Gloria Blumenthal Cancer Center, Paramus, New Jersey, United States of America.

ABSTRACT
The purpose of this study is to evaluate cytokine expression by peripheral blood mononuclear cells (PBMC) from stage I lung cancer patients and to confirm these expression patterns by exposing PBMCs to lung cancer cells in vitro. Five altered cytokines in stage I lung cancer patients (CCL3, IL8, IL1β, CXCL10, sIL2Rα) were identified in plasma from subjects (n = 15) before and after resection using a 30-plex panel protein assay. Gene expression studies using quantitative RT-qPCR were performed on PBMCs from stage I lung cancer patients (n = 62) before and after resection, and compared to non-cancer patients (n = 32) before and after surgery for benign disease. Co-culture experiments that exposed healthy donor PBMCs to lung cancer cells in vitro were performed to evaluate the effect on PBMC cytokine expression. PBMC gene expression of CCL3, IL8 and IL1β was higher in lung cancer patients compared to the same patients at each of four sequential timepoints after removal of their tumors, while CXCL10 and IL2Rα were essentially unchanged. This pattern was also detected when lung cancer patients were compared to non-cancer patients. When non-cancer patients underwent surgery for benign diseases, these cytokine expression changes were not demonstrable. Lung cancer cell lines, but not benign bronchial epithelial cells, induced similar changes in cytokine gene and protein expression by healthy donor PBMCs in an in vitro co-culture system. We conclude that PBMCs from stage I lung cancer patients possess distinct cytokine expression patterns compared to both non-cancer patients, and lung cancer patients following tumor removal. These expression patterns are replicated by healthy donor PBMCs exposed to lung cancer cell lines, but not benign bronchial epithelial cells in vitro. These findings have implications for understanding the immune response to lung cancer.

Show MeSH
Related in: MedlinePlus