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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

Modulation of the main lymphocyte subsets in pancreatic cancer patients undergoing DP with extended lymphadenectomy and mesopancreas exeresis. Frequency of circulating CD3+, CD4+, and CD8+ T (A), NK (B), and B-lymphocyte (D) subsets, in pancreatic cancer patients before surgery (BS), at day 7 (PS7), and at day 30 (PS30) postsurgery, as well as age-matched controls (C). Bars show median and interquartile range. *P < 0.05; **P < 0.005. Distribution and median of NK cell frequency at PS30 in 2-year survivors (black circles) and deceased (white circles) patients, compared with the median of all patients (C, dashed line).
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Figure 1: Modulation of the main lymphocyte subsets in pancreatic cancer patients undergoing DP with extended lymphadenectomy and mesopancreas exeresis. Frequency of circulating CD3+, CD4+, and CD8+ T (A), NK (B), and B-lymphocyte (D) subsets, in pancreatic cancer patients before surgery (BS), at day 7 (PS7), and at day 30 (PS30) postsurgery, as well as age-matched controls (C). Bars show median and interquartile range. *P < 0.05; **P < 0.005. Distribution and median of NK cell frequency at PS30 in 2-year survivors (black circles) and deceased (white circles) patients, compared with the median of all patients (C, dashed line).

Mentions: Before intervention, the frequencies of the major lymphocyte populations (namely, CD3+ T-cells and its main CD4+ and CD8+ subsets, CD3-CD56+ NK cells, and CD19+ B-lymphocytes) were comparable between patients and age-matched controls (Fig. 1). Interestingly, patient NK cell percentage (and absolute concentration, not shown) significantly augmented at day 30, but not at day 7, after surgical intervention (Fig. 1B). In addition, the frequency of circulating B-cells was significantly reduced at the same time point (Fig. 1D). The elevation of NK cells and the diminution of B-cells 30 days after surgery were statistically significant also when compared with control subjects. Differently, the abundance of total T-cells, and of CD4+ and CD8+ subsets, remained comparable to preintervention values (Fig. 1A). Restricting the analysis to patients followed for an overall 2-year period after surgery, survivors show a higher median NK cell frequency at PS30 time point, when compared with deceased patients (Fig. 1C). Thus, surgical removal of the tumor selectively induces the modulation of NK cells and B-lymphocytes, both deeply involved in the immune host defense against cancer. In addition, observational data seem to suggest difference in postsurgery NK cell frequency values among deceased and survivor patients.


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)

Modulation of the main lymphocyte subsets in pancreatic cancer patients undergoing DP with extended lymphadenectomy and mesopancreas exeresis. Frequency of circulating CD3+, CD4+, and CD8+ T (A), NK (B), and B-lymphocyte (D) subsets, in pancreatic cancer patients before surgery (BS), at day 7 (PS7), and at day 30 (PS30) postsurgery, as well as age-matched controls (C). Bars show median and interquartile range. *P < 0.05; **P < 0.005. Distribution and median of NK cell frequency at PS30 in 2-year survivors (black circles) and deceased (white circles) patients, compared with the median of all patients (C, dashed line).
© Copyright Policy
Related In: Results  -  Collection

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

Figure 1: Modulation of the main lymphocyte subsets in pancreatic cancer patients undergoing DP with extended lymphadenectomy and mesopancreas exeresis. Frequency of circulating CD3+, CD4+, and CD8+ T (A), NK (B), and B-lymphocyte (D) subsets, in pancreatic cancer patients before surgery (BS), at day 7 (PS7), and at day 30 (PS30) postsurgery, as well as age-matched controls (C). Bars show median and interquartile range. *P < 0.05; **P < 0.005. Distribution and median of NK cell frequency at PS30 in 2-year survivors (black circles) and deceased (white circles) patients, compared with the median of all patients (C, dashed line).
Mentions: Before intervention, the frequencies of the major lymphocyte populations (namely, CD3+ T-cells and its main CD4+ and CD8+ subsets, CD3-CD56+ NK cells, and CD19+ B-lymphocytes) were comparable between patients and age-matched controls (Fig. 1). Interestingly, patient NK cell percentage (and absolute concentration, not shown) significantly augmented at day 30, but not at day 7, after surgical intervention (Fig. 1B). In addition, the frequency of circulating B-cells was significantly reduced at the same time point (Fig. 1D). The elevation of NK cells and the diminution of B-cells 30 days after surgery were statistically significant also when compared with control subjects. Differently, the abundance of total T-cells, and of CD4+ and CD8+ subsets, remained comparable to preintervention values (Fig. 1A). Restricting the analysis to patients followed for an overall 2-year period after surgery, survivors show a higher median NK cell frequency at PS30 time point, when compared with deceased patients (Fig. 1C). Thus, surgical removal of the tumor selectively induces the modulation of NK cells and B-lymphocytes, both deeply involved in the immune host defense against cancer. In addition, observational data seem to suggest difference in postsurgery NK cell frequency values among deceased and survivor patients.

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