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

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Abstract

Introduction: Cancer heterogeneity and degree of intra-tumoral immune cells represent variables affecting overall survival (OS). The present study investigated the impact of natural killer (NK) and T cells infiltrating colorectal liver metastases (CLM) in patients undergoing hepatectomy after neoadjuvant chemotherapy. Methods: The frequencies of intra-tumoral, marginal, and peritumoral CD3+ T and NKp46+ NK cells were determined for 121 patients. OS was assessed in relation to prognostic factors. Results: At univariate analysis, several variables, including T and N of the primary tumor, metachronous CLM, radiological response, and higher density of intra-tumoral CD3+ T cell (>1%/mm2) and of NKp46+ NK cells (>1 cell/mm2), were associated with OS. Only increased frequencies of intra-tumoral CD3+ T cells (p = 0.005) and NKp46+ NK cells (p = 0.004) correlated with OS at multivariate analysis. The logistic regression revealed that metachronous CLM (OR = 2.781; p = 0.002), the use of an epidermal growth factor receptor inhibitor (OR = 3.891; p = 0.001), and radiological response (OR = 3.219; p = 0.001) were associated with higher infiltration of these cells. Conclusions: 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.

Original languageEnglish
Pages (from-to)1226-1236
Number of pages11
JournalJournal of Gastrointestinal Surgery
Volume21
Issue number8
DOIs
Publication statusPublished - Aug 1 2017

Fingerprint

Natural Killer T-Cells
Neoplasm Metastasis
Survival
Liver
Natural Killer Cells
T-Lymphocytes
Drug Therapy
Hepatectomy
Epidermal Growth Factor Receptor
Colorectal Neoplasms
Multivariate Analysis
Logistic Models
Physicians
Neoplasms

Keywords

  • Chemotherapy
  • Colorectal liver metastases
  • Immune response to colorectal liver metastases
  • Natural killer cells
  • T cells

ASJC Scopus subject areas

  • Surgery
  • Gastroenterology

Cite this

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title = "Increased Infiltration of Natural Killer and T Cells in Colorectal Liver Metastases Improves Patient Overall Survival",
abstract = "Introduction: Cancer heterogeneity and degree of intra-tumoral immune cells represent variables affecting overall survival (OS). The present study investigated the impact of natural killer (NK) and T cells infiltrating colorectal liver metastases (CLM) in patients undergoing hepatectomy after neoadjuvant chemotherapy. Methods: The frequencies of intra-tumoral, marginal, and peritumoral CD3+ T and NKp46+ NK cells were determined for 121 patients. OS was assessed in relation to prognostic factors. Results: At univariate analysis, several variables, including T and N of the primary tumor, metachronous CLM, radiological response, and higher density of intra-tumoral CD3+ T cell (>1{\%}/mm2) and of NKp46+ NK cells (>1 cell/mm2), were associated with OS. Only increased frequencies of intra-tumoral CD3+ T cells (p = 0.005) and NKp46+ NK cells (p = 0.004) correlated with OS at multivariate analysis. The logistic regression revealed that metachronous CLM (OR = 2.781; p = 0.002), the use of an epidermal growth factor receptor inhibitor (OR = 3.891; p = 0.001), and radiological response (OR = 3.219; p = 0.001) were associated with higher infiltration of these cells. Conclusions: 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.",
keywords = "Chemotherapy, Colorectal liver metastases, Immune response to colorectal liver metastases, Natural killer cells, T cells",
author = "Matteo Donadon and Kelly Hudspeth and Matteo Cimino and {Di Tommaso}, Luca and Max Preti and Paolo Tentorio and Massimo Roncalli and Domenico Mavilio and Guido Torzilli",
year = "2017",
month = "8",
day = "1",
doi = "10.1007/s11605-017-3446-6",
language = "English",
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pages = "1226--1236",
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TY - JOUR

T1 - Increased Infiltration of Natural Killer and T Cells in Colorectal Liver Metastases Improves Patient Overall Survival

AU - Donadon, Matteo

AU - Hudspeth, Kelly

AU - Cimino, Matteo

AU - Di Tommaso, Luca

AU - Preti, Max

AU - Tentorio, Paolo

AU - Roncalli, Massimo

AU - Mavilio, Domenico

AU - Torzilli, Guido

PY - 2017/8/1

Y1 - 2017/8/1

N2 - Introduction: Cancer heterogeneity and degree of intra-tumoral immune cells represent variables affecting overall survival (OS). The present study investigated the impact of natural killer (NK) and T cells infiltrating colorectal liver metastases (CLM) in patients undergoing hepatectomy after neoadjuvant chemotherapy. Methods: The frequencies of intra-tumoral, marginal, and peritumoral CD3+ T and NKp46+ NK cells were determined for 121 patients. OS was assessed in relation to prognostic factors. Results: At univariate analysis, several variables, including T and N of the primary tumor, metachronous CLM, radiological response, and higher density of intra-tumoral CD3+ T cell (>1%/mm2) and of NKp46+ NK cells (>1 cell/mm2), were associated with OS. Only increased frequencies of intra-tumoral CD3+ T cells (p = 0.005) and NKp46+ NK cells (p = 0.004) correlated with OS at multivariate analysis. The logistic regression revealed that metachronous CLM (OR = 2.781; p = 0.002), the use of an epidermal growth factor receptor inhibitor (OR = 3.891; p = 0.001), and radiological response (OR = 3.219; p = 0.001) were associated with higher infiltration of these cells. Conclusions: 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.

AB - Introduction: Cancer heterogeneity and degree of intra-tumoral immune cells represent variables affecting overall survival (OS). The present study investigated the impact of natural killer (NK) and T cells infiltrating colorectal liver metastases (CLM) in patients undergoing hepatectomy after neoadjuvant chemotherapy. Methods: The frequencies of intra-tumoral, marginal, and peritumoral CD3+ T and NKp46+ NK cells were determined for 121 patients. OS was assessed in relation to prognostic factors. Results: At univariate analysis, several variables, including T and N of the primary tumor, metachronous CLM, radiological response, and higher density of intra-tumoral CD3+ T cell (>1%/mm2) and of NKp46+ NK cells (>1 cell/mm2), were associated with OS. Only increased frequencies of intra-tumoral CD3+ T cells (p = 0.005) and NKp46+ NK cells (p = 0.004) correlated with OS at multivariate analysis. The logistic regression revealed that metachronous CLM (OR = 2.781; p = 0.002), the use of an epidermal growth factor receptor inhibitor (OR = 3.891; p = 0.001), and radiological response (OR = 3.219; p = 0.001) were associated with higher infiltration of these cells. Conclusions: 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.

KW - Chemotherapy

KW - Colorectal liver metastases

KW - Immune response to colorectal liver metastases

KW - Natural killer cells

KW - T cells

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U2 - 10.1007/s11605-017-3446-6

DO - 10.1007/s11605-017-3446-6

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JO - Journal of Gastrointestinal Surgery

JF - Journal of Gastrointestinal Surgery

SN - 1091-255X

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