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Effect of surgery on pancreatic tumor-dependent lymphocyte asset: modulation of natural killer cell frequency and cytotoxic function.

Iannone F, Porzia A, Peruzzi G, Birarelli P, Milana B, Sacco L, Dinatale G, Peparini N, Prezioso G, Battella S, Caronna R, Morrone S, Palmieri G, Mainiero F, Chirletti P - Pancreas (2015)

Bottom Line: Tumor burden and invasiveness establish a microenvironment that surgery could alter.This study shows a comprehensive analysis of size, dynamics, and function of peripheral lymphocyte subsets in pancreatic cancer patients before and at different times after duodenopancreatectomy.The NK cell functional ability is altered in presurgery patients; duodenopancreatectomy is associated with short-term impairment of NK function and with a long-term NK cell augmentation and reversion of the aberrant NK behavior, which may impact on immunosurveillance against residual cancer.

View Article: PubMed Central - PubMed

Affiliation: From the *Section of Interdisciplinary Surgery F. Durante, Department of Surgical Sciences, †Department of Molecular Medicine, ‡Istituto Italiano di Tecnologia, CLNS, and §Department of Experimental Medicine, Sapienza University of Rome, Italy.

ABSTRACT

Objectives: Tumor burden and invasiveness establish a microenvironment that surgery could alter. This study shows a comprehensive analysis of size, dynamics, and function of peripheral lymphocyte subsets in pancreatic cancer patients before and at different times after duodenopancreatectomy.

Methods: Lymphocyte frequency and natural cytotoxicity were evaluated by flow cytometry and in vitro assay on peripheral blood from initial and advanced-stage pancreatic cancer patients before (BS), at day 7 (PS7), and at day 30 (PS30) after surgery.

Results: An increase in natural killer (NK) cells and the diminution of B-cells occurred at PS30, whereas cytotoxicity decreased at PS7. The positive correlation between NK frequency and cytotoxicity at BS and PS7 revealed an altered NK behavior. The elevation of NK cell frequency at PS30, an initial defect in CD56bright NK, and the aberrant correlation between NK frequency and cytotoxicity remained significant in advanced-stage patients, whereas the diminution of NK cytotoxicity only affected initial stage patients.

Conclusions: The NK cell functional ability is altered in presurgery patients; duodenopancreatectomy is associated with short-term impairment of NK function and with a long-term NK cell augmentation and reversion of the aberrant NK behavior, which may impact on immunosurveillance against residual cancer.

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Related in: MedlinePlus

Dynamics of neutrophil absolute number and NLR in pancreatic cancer patients undergoing DP. Absolute neutrophil counts (A) and NLR (B) in whole blood were obtained in pancreatic cancer patients, at presurgery (BS), at day 7 (PS7), and at day 30 (PS30) postsurgery, as well as age-matched controls (C). *P < 0.05, **P < 0.005, ***P < 0.0001.
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Figure 5: Dynamics of neutrophil absolute number and NLR in pancreatic cancer patients undergoing DP. Absolute neutrophil counts (A) and NLR (B) in whole blood were obtained in pancreatic cancer patients, at presurgery (BS), at day 7 (PS7), and at day 30 (PS30) postsurgery, as well as age-matched controls (C). *P < 0.05, **P < 0.005, ***P < 0.0001.

Mentions: Finally, we also assessed the impact of surgical intervention on systemic inflammation biomarkers, to better evaluate the role of the inflammatory microenvironment in the alteration of NK cell biology. Data reported in Figure 5 show that blood neutrophil concentration, an inflammation marker, and the neutrophil/lymphocyte ratio (NLR), which integrates information on the inflammatory milieu and physiological stress, dramatically increase 7 days after surgery and are close to normalization 30 days after surgery.


Effect of surgery on pancreatic tumor-dependent lymphocyte asset: modulation of natural killer cell frequency and cytotoxic function.

Iannone F, Porzia A, Peruzzi G, Birarelli P, Milana B, Sacco L, Dinatale G, Peparini N, Prezioso G, Battella S, Caronna R, Morrone S, Palmieri G, Mainiero F, Chirletti P - Pancreas (2015)

Dynamics of neutrophil absolute number and NLR in pancreatic cancer patients undergoing DP. Absolute neutrophil counts (A) and NLR (B) in whole blood were obtained in pancreatic cancer patients, at presurgery (BS), at day 7 (PS7), and at day 30 (PS30) postsurgery, as well as age-matched controls (C). *P < 0.05, **P < 0.005, ***P < 0.0001.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4358707&req=5

Figure 5: Dynamics of neutrophil absolute number and NLR in pancreatic cancer patients undergoing DP. Absolute neutrophil counts (A) and NLR (B) in whole blood were obtained in pancreatic cancer patients, at presurgery (BS), at day 7 (PS7), and at day 30 (PS30) postsurgery, as well as age-matched controls (C). *P < 0.05, **P < 0.005, ***P < 0.0001.
Mentions: Finally, we also assessed the impact of surgical intervention on systemic inflammation biomarkers, to better evaluate the role of the inflammatory microenvironment in the alteration of NK cell biology. Data reported in Figure 5 show that blood neutrophil concentration, an inflammation marker, and the neutrophil/lymphocyte ratio (NLR), which integrates information on the inflammatory milieu and physiological stress, dramatically increase 7 days after surgery and are close to normalization 30 days after surgery.

Bottom Line: Tumor burden and invasiveness establish a microenvironment that surgery could alter.This study shows a comprehensive analysis of size, dynamics, and function of peripheral lymphocyte subsets in pancreatic cancer patients before and at different times after duodenopancreatectomy.The NK cell functional ability is altered in presurgery patients; duodenopancreatectomy is associated with short-term impairment of NK function and with a long-term NK cell augmentation and reversion of the aberrant NK behavior, which may impact on immunosurveillance against residual cancer.

View Article: PubMed Central - PubMed

Affiliation: From the *Section of Interdisciplinary Surgery F. Durante, Department of Surgical Sciences, †Department of Molecular Medicine, ‡Istituto Italiano di Tecnologia, CLNS, and §Department of Experimental Medicine, Sapienza University of Rome, Italy.

ABSTRACT

Objectives: Tumor burden and invasiveness establish a microenvironment that surgery could alter. This study shows a comprehensive analysis of size, dynamics, and function of peripheral lymphocyte subsets in pancreatic cancer patients before and at different times after duodenopancreatectomy.

Methods: Lymphocyte frequency and natural cytotoxicity were evaluated by flow cytometry and in vitro assay on peripheral blood from initial and advanced-stage pancreatic cancer patients before (BS), at day 7 (PS7), and at day 30 (PS30) after surgery.

Results: An increase in natural killer (NK) cells and the diminution of B-cells occurred at PS30, whereas cytotoxicity decreased at PS7. The positive correlation between NK frequency and cytotoxicity at BS and PS7 revealed an altered NK behavior. The elevation of NK cell frequency at PS30, an initial defect in CD56bright NK, and the aberrant correlation between NK frequency and cytotoxicity remained significant in advanced-stage patients, whereas the diminution of NK cytotoxicity only affected initial stage patients.

Conclusions: The NK cell functional ability is altered in presurgery patients; duodenopancreatectomy is associated with short-term impairment of NK function and with a long-term NK cell augmentation and reversion of the aberrant NK behavior, which may impact on immunosurveillance against residual cancer.

Show MeSH
Related in: MedlinePlus