Lymph nodes may be a source for immunetherapy in gastric cancer.

Paula Baraúna Assumpção,Erika Couto Canelas,Ana Anaissi,Paulo Assumpção,João Felipe Acioli,Geraldo Ishak,Aline Cruz Ramos,Sidney Santos,Samia Demachki

doi:10.18632/oncotarget.27578

Paula Baraúna Assumpção, Erika Couto Canelas + Show 7 more

Open Access

https://doi.org/10.18632/oncotarget.27578

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Abstract

Background: adoptive immunotherapy is a promising cancer therapy. Immune cells are capable of recognizing and destroying cancer cells and represent a powerful strategy, however, this approach remains technically complicated, due to the need to select and isolate immune cells from these, present cancer antigens to those cells, expanding and reinjecting them. Lymph nodes recovered during gastric cancer surgery may represent an option for immunotherapy, since they harbor an enormous amount of immune cells, which have already been presented to cancer antigens. The advantage of selecting only cancer-negative lymph has not been determined yet. The status of immune checkpoints in the immune cells within the lymph nodes was analyzed in order to try to solve this problem.Materials and Methods: Tissue microarrays were constructed and automated immunostaining for PD-1 and PD-L1 was performed on 143 lymph nodes from 70 patients with gastric adenocarcinoma.Results: In positive nodes, PD-L1 was only positivity in cancer cells (6%) and PD-1 was positive for B lymphocytes (60%), T lymphocytes (70%) and one case in cancer cells (2.5%). In negative nodes, most cases were positive for PD-1 in B (73.1%) and T (71.65%) lymphocytes.Conclusions: Expression of PD-1 and PD-L1 in gastric cancer lymph nodes was demonstrated for the first time. PD-1 is expressed in positive and negative nodes, which could activate the PD-1 pathway. Lymphocytes from tumor-free lymph nodes were negative for PD-L1, and this might represent an advantage for selecting these lymph nodes as a potential source of immune cells for adoptive immunotherapy.

Highlights

Elements of the immune repertoire have gained increased attention since “avoidance of immune response” as one of the hallmarks of cancer [1] and introduction of immune check point therapy for diverse cancer types [2,3,4,5]
In positive nodes, PD-L1 was only positivity in cancer cells (6%) and PD-1 was positive for B lymphocytes (60%), T lymphocytes (70%) and one case in cancer cells (2.5%)
Expression of PD-1 and PD-L1 in gastric cancer lymph nodes was demonstrated for the first time

Summary

Introduction

Elements of the immune repertoire have gained increased attention since “avoidance of immune response” as one of the hallmarks of cancer [1] and introduction of immune check point therapy for diverse cancer types [2,3,4,5]. The resection of regional lymph nodes in gastric cancer surgery is considered one of the most relevant advances, since it seems to be associated with benefits both in the reduction of local recurrence and probably in terms of survival [12,13,14]. The enlargement of regional lymph nodes occurs due to the clonal expansion of lymphocytes that were exposed to immunogenic tumor cells, and as a consequence, became able to identify these tumor cells and eliminate them. These lymph nodes are probably not enemies that should definitely be discarded, but rather, they may be useful elements that can help control the disease. The possibility for the selection of tumor-free lymph nodes, as will be discussed below, should represent an extra advantage that should be considered in the setting of adoptive immunotherapy

Methods

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