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

  • 2016 SSAT Plenary Presentation
  • Published:
Journal of Gastrointestinal Surgery Aims and scope

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.

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Author information

Author notes

  1. Matteo Donadon and Kelly Hudspeth equally contributed as first authors.

  2. Domenico Mavilio and Guido Torzilli equally contributed as senior authors.

Authors and Affiliations

  1. Department of Hepatobiliary and General Surgery, Humanitas University, Humanitas Clinical and Research Center, Via Manzoni 56, 20089, Rozzano, Milan, Italy

    Matteo Donadon, Matteo Cimino & Guido Torzilli

  2. Laboratory of Hepatobiliary Surgery, Humanitas University, Humanitas Clinical and Research Center, Rozzano, Milan, Italy

    Matteo Donadon, Matteo Cimino & Guido Torzilli

  3. Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy

    Kelly Hudspeth, Max Preti, Paolo Tentorio & Domenico Mavilio

  4. Department of Pathology, Humanitas University, Humanitas Clinical and Research Center, Rozzano, Milan, Italy

    Luca Di Tommaso & Massimo Roncalli

  5. Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy

    Domenico Mavilio

Authors
  1. Matteo Donadon
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  2. Kelly Hudspeth
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  4. Luca Di Tommaso
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  8. Domenico Mavilio
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  9. Guido Torzilli
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Contributions

Conception and Design: M. Donadon, D. Mavilio

Development of Methodology: K. Hudspeth, L. Di Tommaso, D. Mavilio

Acquisition of Data: M. Donadon, K. Hudspeth, M. Cimino, L. Di Tommaso, M. Preti, P. Tentorio, M. Roncalli

Analysis and Interpretation of Data: M. Donadon, K. Hudspeth, D. Mavilio

Writing, review, and/or revision of the manuscript: M. Donadon, K. Hudspeth, D. Mavilio

Study Supervision: D. Mavilio. G. Torzilli

Corresponding authors

Correspondence to Domenico Mavilio or Guido Torzilli.

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Funding

This work was supported by the Italian Association for Cancer Research (AIRC IG 14687 to D.M.) and by the intramural research program of Humanitas Clinical and Research Center to M.D., M.C., D.M., and G.T. K.H. is the recipient of a fellowship from the “Fondazione Umberto Veronesi.”

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Meeting presentation

Presented during the plenary section at the 2016 SSAT Meeting in San Diego, CA, USA.

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Donadon, M., Hudspeth, K., Cimino, M. et al. Increased Infiltration of Natural Killer and T Cells in Colorectal Liver Metastases Improves Patient Overall Survival. J Gastrointest Surg 21, 1226–1236 (2017). https://doi.org/10.1007/s11605-017-3446-6

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  • DOI: https://doi.org/10.1007/s11605-017-3446-6

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