Increased Infiltration of Natural Killer and T Cells in Colorectal Liver Metastases Improves Patient Overall Survival

Donadon, Matteo; Hudspeth, Kelly; Cimino, Matteo; Tommaso, Luca Di; Preti, Max; Tentorio, Paolo; Roncalli, Massimo; Mavilio, Domenico; Torzilli, Guido

doi:10.1007/s11605-017-3446-6

Cited by 67 publications

(69 citation statements)

References 36 publications

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“…Consistently, it is in fact well known that human liver is highly enriched of cytotoxic antitumor lymphocytes including T and NK cells that exert immune-surveillance against cancer (72,84,85). Recently, also our group has showed how the presence of intratumoral infiltration of NK cells was an independent prognostic factor favoring overall survival after resection of CLM (86). Those data and results support how the host immune system represents an emerging hallmark of cancer (87) which should not be any more left to exploratory translational researches while it should be routinely considered in daily clinical practice.…”

Section: The Role Of the Host Immune Systemsupporting

confidence: 54%

Search for Theragnostic Biomarkers in Colorectal Liver Metastases: Focus on the Host Immune Cells

Donadon¹,

Soldani²,

Franceschini³

et al. 2017

SGO

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The prognostic factors of patients with colorectal liver metastases (CLM) have been traditionally searched among the factors related to the primary colorectal tumor or to CLM. While many different scoring systems have been developed based on those traditional clinic-pathological factors, there has been the introduction of genetic biomarkers that added a theragnostic perspective. More recently, other important factors, such as those related to the host immune system, have been proposed as new determinants of prognosis of CLM patients. We herein review the current prognostic factors of CLM patients focusing on the burgeoning shifting paradigm of prognostication that relies on the host immune system.

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Section: The Role Of the Host Immune Systemsupporting

confidence: 54%

Search for Theragnostic Biomarkers in Colorectal Liver Metastases: Focus on the Host Immune Cells

Donadon¹,

Soldani²,

Franceschini³

et al. 2017

SGO

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“…Several investigators have reported that patients with a relatively dense infiltration of malignant tumors by NK cells showed better clinical outcomes 18, 35, 36. Outcomes of NK cell‐target cell interactions are regulated by a fine integrative balance between inhibitory and activating receptors expressed on NK cells and their ligands on target cells 37.…”

Section: Discussionmentioning

confidence: 99%

“…The activation signal resulting from the engagement of NKG2D‐DAP10 overrides the inhibitory signal from MHC class I molecules leading to target cell lysis 30, 42. Reportedly, high density of intratumoral NKp46‐expressing NK cells was associated with OS in CRLM patients who received neoadjuvant chemotherapy 18. In this study, the expression of activation markers/effector molecules on both peripheral and liver NK cells of patients treated with neoadjuvant chemotherapy was enhanced compared with that in patients who did not receive chemotherapy; however, the proportion of NK cells among LMNC was reduced.…”

Section: Discussionmentioning

confidence: 99%

“…Although the influence of surgery on immune surveillance against cancer cells has been occasionally investigated, the influence of chemotherapy on that remains to be elucidated. Studies have reported that the presence of tumor‐infiltrating immune cells, such as natural killer (NK) cells and T cells, in CRLM patients improved the overall survival (OS) 6, 18. NK cells are part of the innate immune system and may provide a first line of defense against neoplastic cells by exerting an effector function without the necessity for priming 19.…”

Section: Introductionmentioning

confidence: 99%

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Effect of bevacizumab plus XELOX (CapeOX) chemotherapy on liver natural killer cell activity in colorectal cancer with resectable liver metastasis

Hirata

Ishiyama

Tanaka

et al. 2018

Annals of Gastroent Surgery

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AimWe investigated the chemotherapy effect of resectable colorectal cancer with liver metastasis (CRLM) on the function of intrahepatic immune cells.MethodsWe classified patients into adjuvant chemotherapy (bevacizumab+CapeOX) after hepatectomy group (group A) and neoadjuvant chemotherapy followed by hepatectomy group (group B), and collected peripheral blood mononuclear cells (PBMC) and liver mononuclear cells (LMNC) to ascertain phenotypic and functional differences.ResultsThere were no significant differences in lymphocyte fractions of either PBMC or LMNC between groups, except for the significantly lower percentage of natural killer (NK) cells in LMNC in group B than in group A. Significantly higher percentage of natural‐killer group 2, member D (NKG2D)‐ positive NK cells in PBMC and percentage of tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL)‐, NKp30‐, and signal regulatory protein β (SIRPβ)‐positive NK cells in LMNC were found in group B. Furthermore, significantly higher expressions of NKG2D and SIRPβ in peripheral blood NK cells and of NKp46 and CD122 in liver NK cells were found in group B. When LMNC were incubated with interleukin (IL)‐2 in vitro, no difference was observed in the expression of these molecules in NK cells between groups. Consistently, there was no difference in the cytotoxic activity of those LMNC against a colon adenocarcinoma cell line between groups.ConclusionColorectal cancer with liver metastasis patients treated with neoadjuvant chemotherapy showed enhanced expression of activation markers on peripheral blood and liver NK cells in comparison with patients who did not receive therapy; however, the difference in those function remains unclear. These results suggest that neoadjuvant chemotherapy does not have a negative impact on intrahepatic immune cells in resectable CRLM patients.

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“…Other innate immune cells such as NK cells function in immune surveillance, vigilant for metastatic cells. There is a general consensus that NK cell cytotoxicity exerts a pivotal role against metastatic dissemination; indeed, an inverse correlation between metastasis and cytotoxic NK cell activity has been observed in renal , prostate , pancreatic , gastric , melanoma , breast , colorectal and lung cancer patients . Notably, the in vivo NK cell depletion by specific antibodies against NK cell receptors, results in increased metastatic burden in immunocompetent mice .…”

Section: Immune Surveillance During Metastasismentioning

confidence: 99%

Innate and acquired immune surveillance in the postdissemination phase of metastasis

2017

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Metastasis is responsible for the majority of death in cancer patients. Of the different steps in the metastasis cascade, the postdissemination phase is perhaps one of the least understood. Many factors, both from the disseminated tumor cells and the microenvironment, impact the success of the metastatic outgrowth. In this article, we discuss the interactions between colonizing cancer cells and immune cells in the period between vascular arrest in a secondary organ and metastatic outgrowth. We address the ambiguity in the findings of current research regarding the role of immune cells in regulating the metastatic microenvironment, and their hand in determining cancer cell fate.

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Increased Infiltration of Natural Killer and T Cells in Colorectal Liver Metastases Improves Patient Overall Survival

Abstract: High frequencies of NK and T cells in response to chemotherapy predict OS in CLM patients. These findings provide important insights that can help physicians to choose the best treatment option and adopt more predictive follow-up strategies for patients with CLM.

Cited by 67 publications

References 36 publications

Search for Theragnostic Biomarkers in Colorectal Liver Metastases: Focus on the Host Immune Cells

Search for Theragnostic Biomarkers in Colorectal Liver Metastases: Focus on the Host Immune Cells

Effect of bevacizumab plus XELOX (CapeOX) chemotherapy on liver natural killer cell activity in colorectal cancer with resectable liver metastasis

Innate and acquired immune surveillance in the postdissemination phase of metastasis

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