Immunoscore and personification of chemotherapeutic treatment in patients with gastric cancer

Abstract

Background. There are a few indications known in the world to administer immunotherapy (IT) via immune checkpoint inhibitors (ICIs). Prescribing IT by means of ICIs in gastric cancer (GC) results from PDL1 ligand expression on tumor cells; high tumor mutation burden; GC with microsatellite instability MSI-h or DNA mismatch repair (MMR) failure; T-killer immunoscore (IS). Purpose. To study the composition of the immunocellular phenotype of gastric malignancies. Materials and methods. The paper presents the outcomes of a clinical study conducted at the premises of Thoracic Tumors Research Department of National Cancer Institute and Abdominal Oncosurgery Department of Municipal Non-Profit Enterprise “Odessa Regional Oncology Dispensary” of Odessa Regional Council enrolling 221 patients operated on for gastric cancer within the period from 2007 to 2013. The average age was 60.88 ± 10.5, men – 180, women – 41. A total of 143 gastrectomies and 78 distal subtotal resections were performed. The study group of patients to investigate IS consisted of 22 patients with gastric cancer. At the first stage, the density of immunocompetent TILs or TIMs were determined, where TILs quantified tumor-infiltrating lymphocytes and TIMs counted the number of tumor-infiltrating macrophages. The second step was assessing the severity of infiltration by immune cells of two compartments: the central areas of the tumor (CT) and around the edge of the tumor invasion (IM), i. e. in the peritumoral stroma. Results and discussion. All patients included in the study were radically operated on. The tumors removed during surgery were examined by means of immunoscore. A particularly high correlation was observed between PD-L1 expression in cells and CD8 T-lymphocytes in tumor nest – 0.81. Immunoscore effect on the prognosis was 0.64. A negative high correlation was assessed between the concentration of M2 CD163 macrophages in the tumor and the metastases to regional lymph nodes – 0.65. A particularly high correlation between the concentration of CD3 and CD8 in the central areas of the tumor reaching 0.95. A particularly high correlation between PD-L1 expression in cells and CD3 cells in tumor nest – 0.84. The correlation between CD3 and CD8 in the tumor stroma was particularly high, 0.87. Conclusions. The study of immunoscore is essential both in terms of the impact on patient survival, as a prognostic factor, and with a view to more active administering and using immune-targeted drugs in the future.

Keywords

• gastric cancer, oncoproteins, immunohistochemical study, immunoscore