Matteo Donadon1,2, Kelly Hudspeth3, Matteo Cimino1,2, Luca Di Tommaso4, Max Preti3, Paolo Tentorio3, Massimo Roncalli4, Domenico Mavilio5,6, Guido Torzilli7,8. 1. Department of Hepatobiliary and General Surgery, Humanitas University, Humanitas Clinical and Research Center, Via Manzoni 56, 20089, Rozzano, Milan, Italy. 2. Laboratory of Hepatobiliary Surgery, Humanitas University, Humanitas Clinical and Research Center, Rozzano, Milan, Italy. 3. Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy. 4. Department of Pathology, Humanitas University, Humanitas Clinical and Research Center, Rozzano, Milan, Italy. 5. Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy. domenico.mavilio@humanitas.it. 6. Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy. domenico.mavilio@humanitas.it. 7. Department of Hepatobiliary and General Surgery, Humanitas University, Humanitas Clinical and Research Center, Via Manzoni 56, 20089, Rozzano, Milan, Italy. ricercachirurgia.epatobiliare@humanitas.it. 8. Laboratory of Hepatobiliary Surgery, Humanitas University, Humanitas Clinical and Research Center, Rozzano, Milan, Italy. ricercachirurgia.epatobiliare@humanitas.it.
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.
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.
Entities:
Keywords:
Chemotherapy; Colorectal liver metastases; Immune response to colorectal liver metastases; Natural killer cells; T cells
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