Pernambuco Cancer Hospital Brazilian Society of Surgical Oncology (BSSO) Recife, Pernambuco, Brazil
Introduction: Gastric Cancer (GC) is the world's fourth leading cause of cancer-related death. Immune system cells can express inhibition and activation receptors associated with an effective immune response to protein antigens. In this sense, the co-inhibitory molecules PD-1, PD-L1, PD-L2, TIM-3, Gal9, and co-stimulators GITR and GITRL are immune checkpoints and are currently being evaluated as potential targets for new antitumor therapeutic approaches.
Objective: to assess soluble levels of sPD-1, sPD-L1, sPD-L2, sTIM-3, sGal9, sGITR, and sGITRL in GC patients and associate them with disease progression. Methods: >/b> A cross-sectional study was performed on CG patients on treatment for potentially curable in Hospital Cancer Pernambuco between 2017 to 2018. Laboratory analysis was in the Translational Research Laboratory of the Instituto de Medicina Integral Prof. Fernando Figueira (IMIP). Seventy-four patients with GC and 30 healthy controls were included. Plasma levels of sPD-1, sPD-L1, sPD-L2, sTIM-3, sGal9, sGITR, and sGITRL were measured using enzyme-linked immunosorbent assay (ELISA). Mann-Whitney and Kruskal-Wallis tests analyzed medians between two and three groups, respectively. Values of p<0.05 were considered significant. All statistical analysis was performed using GraphPadPrism v6.0.
Results: We found high levels of sPDL1 (p=0.0042), sTIM-3(p=0.0072), sGITR(p=0.0179), and sGITRL(p=0.0055), and low levels of sPD-1(p=0.017), sPDL2(p=0.0003) and sGal9 (p < 0.0001) in patients with GC compared to healthy controls. Lower levels of sGITR in patients with GC who died within the first 24 months compared to the group who survived (p=0.0332). Elevated levels of sPD-1, sTIM-3, and sGal9 in patients with stage IV compared to groups with stages I/II and III. High levels of sPD-L1, sGal9, and sGITRL in patients with tumors located at the esophagogastric junction compared to groups with tumors located in the body (p=0.0303, p=0.0025, p=0.0003, respectively) and in the gastric antrum (p=0.0091 and p =0.0004, p=0.0002, respectively). Smokers (p=0.0109) and alcoholics (p=0.0006) patients had lower levels of sGITRL than non-smokers and non-alcoholics, respectively.
Conclusion: There is an association of sTIM-3 and sGal9 with disease progression and sGITR with death, suggesting that sTIM-3, sGal9, and sGITR may be potential prognostic biomarkers in GC.
.jpg "Luciana Silva, MD (she/her/hers) photo")