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Unbalanced expression of sICOS and sPD-1 correlates with tumor progression in gastric cancer
The activation of T cells plays a central role in antitumor immunity in gastric cancer (GC). The inducible costimulatory molecule (ICOS) is a T cell receptor that primarily transmits positive signals for T cell activation, and it has been associated with poor prognosis in GC. In contrast, the costimulatory molecule programmed death 1 (PD-1) is associated with tumor immune escape through negative regulation of T cells antitumor immune response, and it has been found to be a very promising therapeutic target.
This study aimed to analyze the expression of the soluble form of costimulatory molecules ICOS (sICOS) and PD-1 (sPD-1) in peripheral blood of gastric cancer patients and evaluate its roles as possible prognostic biomarkers and therapeutic targets for gastric cancer treatment.
This study enrolled 83 patients with GC and 20 healthy patients. Peripheral blood was collected and serum levels of sICOS and sPD-1 were measured by ELISA assays. GC patients were stratified by TNM staging in early stage (I and II), intermediate (III) and metastatic stage (IV).
Gastric cancer patients had significantly lower levels of sPD-1 (p=0.003) and sICOS (p<0.0001) in comparison with the control group. Patients with early stage GC were more likely to have higher levels of sICOS than patients with stage III (p=0.0005) and stage IV (p=0.02). Conversely, sPD-1 levels presented the inverse pathway: metastatic patients had significantly higher levels of sPD-1 than stage III patients (p=0.0004) and early stage patients (p=0.008).
This is the first study analyzing serum levels of positive costimulatory molecule sICOS and negative costimulatory molecule sPD-1 in patients with gastric cancer. This study demonstrated that early stage GC patients have lower levels of sPD-1 and higher levels of sICOS than advanced stage patients. These results suggest a predominance of positive costimulatory signals in early stages of GC, resulting in an effective antitumor T-cell-mediated immune response, as the opposite occurs in metastatic stages, facilitating tumor immune escape. The imbalance between positive and negative costimulatory signals may have an important role in gastric cancer progression and antitumor immune response. Furthermore, serum levels of sICOS and sPD-1 may serve as prognostic biomarkers as it correlates with advanced GC, and the pathways in which they act may be promising targets for immunotherapy in GC.
gastric cancer, ICOS, PD-1
Trato gastrointestinal alto*
CECÍLIA ARAÚJO CARNEIRO LIMA, MÁRIO RINO MARTINS, ROGÉRIO LUIZ DOS SANTOS, LUCIANA MATA DA SILVA, JERÔNIMO PAULO ASSIS DA SILVA, LEURIDAN CAVALCANTE TORRES, NORA MANOUKIAN FORONES