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Clinical significance of soluble forms of immune checkpoint molecules in advanced esophageal cancer

Juichiro Yoshida¹, Takeshi Ishikawa^2,3, Toshifumi Doi¹

¹Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajiicho Hirokoji Kawaramachi Kamigyo-ku, Kyoto, 602-8566, Japan.

Medical Oncology (Northwood, London, England)

|May 29, 2019

Abstract:

Immune checkpoint molecules are expressed on cancer cells and regulate tumor immunity by binding to ligands on immune cells. Although soluble forms of immune checkpoint molecules have been detected in the blood of patients with some types of tumors, their roles have not been fully elucidated. Soluble PD-L1, PD-1, CD155, LAG3, and CD226 (sPD-L1, sPD-1, sCD155, sLAG3, and sCD226, respectively) were measured in the sera of 47 patients with advanced esophageal cancer and compared with those of 24 control subjects. Pretreatment levels of sPD-1 and sCD155 were significantly higher in the patients with cancer than in the control subjects (P = 0.023, P = 0.001). The sPD-1 levels tended to be higher in the patients with lymph node metastasis, a large tumor diameter, and higher levels of serum SCC antigen (P = 0.150, P = 0.189, and P = 0.078, respectively). However, higher levels of sCD155 were associated with a better response to chemotherapy and favorable overall survival (P = 0.111 and P = 0.068, respectively). After 2 courses of chemotherapy, the levels of sCD155 and sCD226 were significantly increased (P < 0.001 and P = 0.002, respectively). Moreover, the increase in sCD226 during chemotherapy was associated with poor treatment response (P = 0.019). sPD-1 levels are possibly dependent on the tumor aggressiveness of the esophageal cancer. Furthermore, the pretreatment levels of sCD155 and kinetic change of sCD226 after chemotherapy may be used as biomarkers of the treatment response and prognosis in patients with esophageal cancer.

Insights

Soluble immune checkpoint molecules like sPD-1 and sCD155 are elevated in esophageal cancer patients. These markers, particularly sCD155 and sCD226, may indicate treatment response and prognosis.

Area of Science:

Immunology
Oncology
Biochemistry

Background:

Immune checkpoint molecules regulate anti-tumor immunity.
Soluble forms of these molecules are found in cancer patients, but their roles are unclear.
Investigating soluble immune checkpoints in esophageal cancer is crucial for understanding tumor immunity and treatment response.

Purpose of the Study:

To measure and compare serum levels of soluble immune checkpoint molecules (sPD-L1, sPD-1, sCD155, sLAG3, sCD226) in advanced esophageal cancer patients and healthy controls.
To explore the association of these soluble markers with clinicopathological features and treatment outcomes.
To evaluate the dynamic changes of these markers during chemotherapy and their prognostic significance.

Main Methods:

Serum samples were collected from 47 advanced esophageal cancer patients and 24 controls.
Levels of soluble programmed death-ligand 1 (sPD-L1), soluble programmed cell death protein 1 (sPD-1), soluble CD155, soluble Lymphocyte-activation gene 3 (sLAG3), and soluble CD226 were quantified.
Statistical analyses were performed to compare levels between groups and correlate with clinical data and treatment response.

Main Results:

Pretreatment serum levels of sPD-1 and sCD155 were significantly higher in esophageal cancer patients compared to controls.
Elevated sPD-1 levels showed a trend towards association with tumor aggressiveness (lymph node metastasis, tumor diameter, SCC antigen).
Higher pretreatment sCD155 levels were associated with better chemotherapy response and overall survival.
Serum levels of sCD155 and sCD226 significantly increased after chemotherapy.
An increase in sCD226 during chemotherapy correlated with a poor treatment response.

Conclusions:

sPD-1 levels may reflect tumor aggressiveness in esophageal cancer.
Pretreatment sCD155 levels and the change in sCD226 during chemotherapy show potential as biomarkers for predicting treatment response and prognosis in esophageal cancer patients.

Read full analysis

Keywords:

Biomarker Esophageal cancer Soluble immune checkpoint molecules

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