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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

Distinct alterations in the dynamics of CD56dim and CD56bright NK cell subsets of initial and advanced-stage cancer patients, at presurgery and postsurgery. Frequency of CD56bright (A and D) and CD56dim (B and E) NK cell subsets in PB of initial (A and B) and advanced (D and E) cancer stage patients, before surgery (BS), at day 7 (PS7), and at day 30 (PS30) postsurgery, as well as age-matched controls. Bars show median and interquartile range. Scatter plots representing the percentage of cytotoxicity versus CD56dim NK cell frequency in each initial (C) and advanced (F) cancer stage patient, before surgery (BS, black symbols and line), at day 7 (PS7, gray symbols and line), and at day 30 (PS30, white symbols) postsurgery, as well as age-matched controls (x symbols). Lines in the plots represent the linear regression for any given pair of variables. *P < 0.05, **P < 0.005, ***P < 0.0001.
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Figure 4: Distinct alterations in the dynamics of CD56dim and CD56bright NK cell subsets of initial and advanced-stage cancer patients, at presurgery and postsurgery. Frequency of CD56bright (A and D) and CD56dim (B and E) NK cell subsets in PB of initial (A and B) and advanced (D and E) cancer stage patients, before surgery (BS), at day 7 (PS7), and at day 30 (PS30) postsurgery, as well as age-matched controls. Bars show median and interquartile range. Scatter plots representing the percentage of cytotoxicity versus CD56dim NK cell frequency in each initial (C) and advanced (F) cancer stage patient, before surgery (BS, black symbols and line), at day 7 (PS7, gray symbols and line), and at day 30 (PS30, white symbols) postsurgery, as well as age-matched controls (x symbols). Lines in the plots represent the linear regression for any given pair of variables. *P < 0.05, **P < 0.005, ***P < 0.0001.

Mentions: To investigate in depth the NK cell compartment in initial and advanced-stage pancreatic cancer patients, we analyzed the 2 main functionally and phenotypically different NK cell subsets, namely, CD56bright (equipped with a low cytotoxic potential) and CD56dim (highly cytotoxic and representing the vast majority of PB NK cells). Strikingly, in the percentage of CD56bright NK cells in advanced-stage, but not in early-stage, patients was basally lower than controls and attained normal levels early after surgical intervention (Figs. 4A, D). No statistically significant differences could be found in the representativeness of CD56dim NK cells, in either group of patients (Figs. 4B, E). In addition, the extent of cytotoxic activity in individual early-stage patients bore no correlation with the frequency of CD56dim NK cells at any time points, similarly to what occurred in controls (Fig. 4C); at variance, the frequency of CD56dim NK cells significantly correlated with the levels of PBMC cytotoxicity in advanced-stage patients, both at presurgery and at day 7 postsurgery (Fig. 4F).


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)

Distinct alterations in the dynamics of CD56dim and CD56bright NK cell subsets of initial and advanced-stage cancer patients, at presurgery and postsurgery. Frequency of CD56bright (A and D) and CD56dim (B and E) NK cell subsets in PB of initial (A and B) and advanced (D and E) cancer stage patients, before surgery (BS), at day 7 (PS7), and at day 30 (PS30) postsurgery, as well as age-matched controls. Bars show median and interquartile range. Scatter plots representing the percentage of cytotoxicity versus CD56dim NK cell frequency in each initial (C) and advanced (F) cancer stage patient, before surgery (BS, black symbols and line), at day 7 (PS7, gray symbols and line), and at day 30 (PS30, white symbols) postsurgery, as well as age-matched controls (x symbols). Lines in the plots represent the linear regression for any given pair of variables. *P < 0.05, **P < 0.005, ***P < 0.0001.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4358707&req=5

Figure 4: Distinct alterations in the dynamics of CD56dim and CD56bright NK cell subsets of initial and advanced-stage cancer patients, at presurgery and postsurgery. Frequency of CD56bright (A and D) and CD56dim (B and E) NK cell subsets in PB of initial (A and B) and advanced (D and E) cancer stage patients, before surgery (BS), at day 7 (PS7), and at day 30 (PS30) postsurgery, as well as age-matched controls. Bars show median and interquartile range. Scatter plots representing the percentage of cytotoxicity versus CD56dim NK cell frequency in each initial (C) and advanced (F) cancer stage patient, before surgery (BS, black symbols and line), at day 7 (PS7, gray symbols and line), and at day 30 (PS30, white symbols) postsurgery, as well as age-matched controls (x symbols). Lines in the plots represent the linear regression for any given pair of variables. *P < 0.05, **P < 0.005, ***P < 0.0001.
Mentions: To investigate in depth the NK cell compartment in initial and advanced-stage pancreatic cancer patients, we analyzed the 2 main functionally and phenotypically different NK cell subsets, namely, CD56bright (equipped with a low cytotoxic potential) and CD56dim (highly cytotoxic and representing the vast majority of PB NK cells). Strikingly, in the percentage of CD56bright NK cells in advanced-stage, but not in early-stage, patients was basally lower than controls and attained normal levels early after surgical intervention (Figs. 4A, D). No statistically significant differences could be found in the representativeness of CD56dim NK cells, in either group of patients (Figs. 4B, E). In addition, the extent of cytotoxic activity in individual early-stage patients bore no correlation with the frequency of CD56dim NK cells at any time points, similarly to what occurred in controls (Fig. 4C); at variance, the frequency of CD56dim NK cells significantly correlated with the levels of PBMC cytotoxicity in advanced-stage patients, both at presurgery and at day 7 postsurgery (Fig. 4F).

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