Effect of Surgery on Pancreatic Tumor-Dependent Lymphocyte Asset

Iannone, F.; Porzia, Alessandra; Peruzzi, Giovanna; Birarelli, P; Milana, Bernardina; Sacco, L.; Dinatale, Giuseppe; Peparini, Nadia; Prezioso, Giampaolo; Battella, Simone; Caronna, Roberto; Morrone, Stefania; Palmieri, Gabriella; Mainiero, Fabrizio; Chirletti, Piero

doi:10.1097/mpa.0000000000000288

Cited by 32 publications

(16 citation statements)

References 48 publications

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“…Surgery has been described to cause NK cell dysfunction, 50 but these effects were of limited duration, with cytotoxic capacity returning to pre-surgery values after approximately 30 d 47 . In our cohort of STS patients, blood samples were taken at least 4 weeks after surgery.…”

Section: Discussionmentioning

confidence: 99%

Progressive natural killer cell dysfunction associated with alterations in subset proportions and receptor expression in soft-tissue sarcoma patients

et al. 2016

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Immunotherapy is currently investigated as treatment option in many types of cancer. So far, results from clinical trials have demonstrated that significant benefit from immunomodulatory therapies is restricted to patients with select histologies. To broaden the potential use of these therapies, a deeper understanding for mechanisms of immunosuppression in patients with cancer is needed. Soft-tissue sarcoma (STS) presents a medical challenge with significant mortality even after multimodal treatment. We investigated function and immunophenotype of peripheral natural killer (NK) cells from chemotherapy-naive STS patients (1st line) and STS patients with progression or relapse after previous chemotherapeutic treatment (2nd line). We found NK cells from peripheral blood of both STS patient cohorts to be dysfunctional, being unable to lyse K562 target cells while NK cells from renal cell cancer (RCC) patients did not display attenuated lytic activity. Ex vivo stimulation of NK cells from STS patients with interleukin-2 plus TKD restored cytotoxic function. Furthermore, altered NK cell subset composition with reduced proportions of CD56dim cells could be demonstrated, increasing from 1st- to 2nd-line patients. 2nd-line patients additionally displayed significantly reduced expression of receptors (NKG2D), mediators (CD3ζ), and effectors (perforin) of NK cell activation. In these patients, we also detected fewer NK cells with CD57 expression, a marker for terminally differentiated cytotoxic NK cells. Our results elucidate mechanisms of NK cell dysfunction in STS patients with advanced disease. Markers like NKG2D, CD3ζ, and perforin are candidates to characterize NK cells with effective antitumor function for immunotherapeutic interventions.

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Section: Discussionmentioning

confidence: 99%

Progressive natural killer cell dysfunction associated with alterations in subset proportions and receptor expression in soft-tissue sarcoma patients

et al. 2016

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“…The physiological toll and consequences of surgery has direct effects on NK cell function. A study by Iannone et al [ 38 ] showed that NK cell cytotoxicity is significantly decreased ( p = < 0.005) following surgery on post-operation day (POD) 7 in 24 pancreatic cancer patients undergoing duodenopancreatectomies which was not dependent on NK cell number. By POD30, NK cell cytotoxicity was restored [ 38 ].…”

Section: Natural Killer Cell Dysfunction After Surgerymentioning

confidence: 99%

“…A study by Iannone et al [ 38 ] showed that NK cell cytotoxicity is significantly decreased ( p = < 0.005) following surgery on post-operation day (POD) 7 in 24 pancreatic cancer patients undergoing duodenopancreatectomies which was not dependent on NK cell number. By POD30, NK cell cytotoxicity was restored [ 38 ]. We have reported a similar phenomenon in CRC surgery patient peripheral blood mononuclear cells (PBMCs) collected before surgery, on POD1, POD3, and POD28.…”

Section: Natural Killer Cell Dysfunction After Surgerymentioning

confidence: 99%

Dysfunctional Natural Killer Cells in the Aftermath of Cancer Surgery

Angka

Khan

Kilgour

et al. 2017

IJMS

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The physiological changes that occur immediately following cancer surgeries initiate a chain of events that ultimately result in a short pro-, followed by a prolonged anti-, inflammatory period. Natural Killer (NK) cells are severely affected during this period in the recovering cancer patient. NK cells play a crucial role in anti-tumour immunity because of their innate ability to differentiate between malignant versus normal cells. Therefore, an opportunity arises in the aftermath of cancer surgery for residual cancer cells, including distant metastases, to gain a foothold in the absence of NK cell surveillance. Here, we describe the post-operative environment and how the release of sympathetic stress-related factors (e.g., cortisol, prostaglandins, catecholamines), anti-inflammatory cytokines (e.g., IL-6, TGF-β), and myeloid derived suppressor cells, mediate NK cell dysfunction. A snapshot of current and recently completed clinical trials specifically addressing NK cell dysfunction post-surgery is also discussed. In collecting and summarizing results from these different aspects of the surgical stress response, a comprehensive view of the NK cell suppressive effects of surgery is presented. Peri-operative therapies to mitigate NK cell suppression in the post-operative period could improve curative outcomes following cancer surgery.

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“…Downregulation of immunity after surgery is known to peak at postoperative day (POD) 3[ 13 ], and the decline in NK cell cytotoxicity has been documented to last until POD 7 to 9, depending on the surgical procedure[ 14 - 16 ]. A decrease in NK cell cytotoxicity following pancreaticoduodenectomy (PD) at POD 7 was also recently reported[ 17 ]. These results indicate that the early postoperative period harbors potential for the initiation of cancer metastasis, either de novo or from pre-existing micrometastasis.…”

Section: Introductionmentioning

confidence: 60%

Negative oncologic impact of poor postoperative pain control in left-sided pancreatic cancer

Min¹,

Chong²,

Hwang³

et al. 2017

WJG

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AIMTo investigate the association between postoperative pain control and oncologic outcomes in resected pancreatic ductal adenocarcinoma (PDAC).METHODSFrom January 2009 to December 2014, 221 patients were diagnosed with PDAC and underwent resection with curative intent. Retrospective review of the patients was performed based on electronic medical records system. One patient without records of numerical rating scale (NRS) pain intensity scores was excluded and eight patients who underwent total pancreatectomy were also excluded. NRS scores during 7 postoperative days following resection of PDAC were reviewed along with clinicopathologic characteristics. Patients were stratified into a good pain control group and a poor pain control group according to the difference in average pain intensity between the early (POD 1, 2, 3) and late (POD 5, 7) postoperative periods. Cox-proportional hazards multivariate analysis was performed to determine association between postoperative pain control and oncologic outcomes.RESULTSA total of 212 patients were dichotomized into good pain control group (n = 162) and poor pain control group (n = 66). Median follow-up period was 17 mo. A negative impact of poor postoperative pain control on overall survival (OS) was observed in the group of patients receiving distal pancreatectomy (DP group; 42.0 mo vs 5.0 mo, P = 0.001). Poor postoperative pain control was also associated with poor disease-free survival (DFS) in the DP group (18.0 mo vs 8.0 mo, P = 0.001). Patients undergoing pancreaticoduodenectomy or pylorus-preserving pancreaticoduodenectomy (PD group) did not show associations between postoperative pain control and oncologic outcomes. Poor patients’ perceived pain control was revealed as an independent risk factor of both DFS (HR = 4.157; 95%CI: 1.938-8.915; P < 0.001) and OS (HR = 4.741; 95%CI: 2.214-10.153; P < 0.001) in resected left-sided pancreatic cancer.CONCLUSIONAdequate postoperative pain relief during the early postoperative period has important clinical implications for oncologic outcomes after resection of left-sided pancreatic cancer.

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Effect of Surgery on Pancreatic Tumor-Dependent Lymphocyte Asset

Cited by 32 publications

References 48 publications

Progressive natural killer cell dysfunction associated with alterations in subset proportions and receptor expression in soft-tissue sarcoma patients

Progressive natural killer cell dysfunction associated with alterations in subset proportions and receptor expression in soft-tissue sarcoma patients

Dysfunctional Natural Killer Cells in the Aftermath of Cancer Surgery

Negative oncologic impact of poor postoperative pain control in left-sided pancreatic cancer

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