Exploration of Digestive Diseases

Special Issue Topic

Immunotherapy for Cancer of Digestive System

Submission Deadline: October 31, 2024

Guest Editor

Prof. Evgeny Imyanitov E-Mail

Saint Petersburg State Pediatric Medical University, Saint Petersburg, Russian Federation

Research Keywords: immune checkpoint inhibitors, microsatellite instability, mismatch repair deficiency, tumor mutation burden, PD-L1, esophageal cancer, gastric cancer, hepatobiliary cancer, colorectal cancer

About the Special Issue

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. These drugs antagonize immune-suppressive molecules and restore antitumor defense. ICIs are currently utilized for the management of a wide variety of gastrointestinal malignancies, including esophageal, gastric, hepatobiliary and colorectal cancers. The administration of ICIs often relies on the evaluation of predictive markers, particularly microsatellite instability (mismatch repair deficiency), tumor mutation burden and PD-L1 expression. ICIs are being intensively investigated in combination with other anticancer drugs, particularly cytotoxic and targeted agents. This issue is dedicated to the discussion on various aspects of immune therapy for gastrointestinal malignancies.

Keywords: immune checkpoint inhibitors, microsatellite instability, mismatch repair deficiency, tumor mutation burden, PD-L1, esophageal cancer, gastric cancer, hepatobiliary cancer, colorectal cancer

Call for Papers

Published Articles

Open Access

Original Article

Immune checkpoint inhibitors in patients with advanced gastric cancer: a multi-institutional retrospective real-world study
Aim: Selecting patients for immunotherapy in metastatic gastric cancer (mGC) in second and subsequent lines remains challenging. The aim of our study is to assess the feasibility of anti-programm [...] Read more.

Aim:

Selecting patients for immunotherapy in metastatic gastric cancer (mGC) in second and subsequent lines remains challenging. The aim of our study is to assess the feasibility of anti-programmed death-ligand 1 (anti-PD-L1) inhibitors in pretreated patients with mGC, and to determine prognostic and predictive biomarkers.

Methods:

We retrospectively analyzed data of 122 patients treated in five oncology centers in Moscow between 2018 and 2023, who received nivolumab or pembrolizumab for advanced gastric cancer. The primary end-point of our study was 6-month progression-free survival (PFS). For multivariate analysis, variables with a value of p < 0.05 obtained in a univariate analysis were selected. The optimal threshold value of the neutrophil-lymphocyte ratio (NLR) as a predictor of the effectiveness of immunotherapy was determined using receiver operating characteristic (ROC) curve analysis.

Results:

Patients with mGC who received immune checkpoint inhibitors (ICIs) were included. 6-month PFS rate was 31.6%. The median PFS (mPFS) and overall survival (mOS) in patients in the high NLR group (NLR ≥ 1.8) were 2 and 4 months; mOS and mPFS in the low NLR group were not achieved (p < 0.001). The presence of ascites (p < 0.001), the administration of ICIs in III–IV lines (p = 0.004), and NLR ≥ 1.8 (p = 0.006) were independent prognostic factors, associated with decrease of OS. The median OS of patients in favorable and unfavorable prognostic groups were 13 months and 2 months, respectively (p < 0.001).

Conclusions:

Ascites, NLR level of ≥ 1.8, and administration of anti-PD-L1 inhibitors were associated with low efficacy of immunotherapy in patients with microsatellite stable mGC. Further research should be planned including patients who did not receive ICIs to determine the prognostic significance of our model.

Anastasia Rays ... Аlexey Tryakin

Published: March 27, 2025 Explor Dig Dis. 2025;4:100568
DOI: https://doi.org/10.37349/edd.2025.100568

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Aim:

Selecting patients for immunotherapy in metastatic gastric cancer (mGC) in second and subsequent lines remains challenging. The aim of our study is to assess the feasibility of anti-programmed death-ligand 1 (anti-PD-L1) inhibitors in pretreated patients with mGC, and to determine prognostic and predictive biomarkers.

Methods:

We retrospectively analyzed data of 122 patients treated in five oncology centers in Moscow between 2018 and 2023, who received nivolumab or pembrolizumab for advanced gastric cancer. The primary end-point of our study was 6-month progression-free survival (PFS). For multivariate analysis, variables with a value of p < 0.05 obtained in a univariate analysis were selected. The optimal threshold value of the neutrophil-lymphocyte ratio (NLR) as a predictor of the effectiveness of immunotherapy was determined using receiver operating characteristic (ROC) curve analysis.

Results:

Patients with mGC who received immune checkpoint inhibitors (ICIs) were included. 6-month PFS rate was 31.6%. The median PFS (mPFS) and overall survival (mOS) in patients in the high NLR group (NLR ≥ 1.8) were 2 and 4 months; mOS and mPFS in the low NLR group were not achieved (p < 0.001). The presence of ascites (p < 0.001), the administration of ICIs in III–IV lines (p = 0.004), and NLR ≥ 1.8 (p = 0.006) were independent prognostic factors, associated with decrease of OS. The median OS of patients in favorable and unfavorable prognostic groups were 13 months and 2 months, respectively (p < 0.001).

Conclusions:

Ascites, NLR level of ≥ 1.8, and administration of anti-PD-L1 inhibitors were associated with low efficacy of immunotherapy in patients with microsatellite stable mGC. Further research should be planned including patients who did not receive ICIs to determine the prognostic significance of our model.

Open Access

Review

Current efficacy of immune checkpoint inhibitors in microsatellite unstable colorectal cancer and potential biomarkers
Microsatellite unstable (MSI) colorectal cancer (CRC) tumors have a high mutational load (particularly frame-shift mutations) that creates numerous neoantigens that are presented to major histocompa [...] Read more.

Microsatellite unstable (MSI) colorectal cancer (CRC) tumors have a high mutational load (particularly frame-shift mutations) that creates numerous neoantigens that are presented to major histocompatibility complex molecules and recognized by T cells. Consequently, MSI tumors have a higher presence of tumor-infiltrating lymphocytes than mismatch repair-proficient tumors. Colorectal cancer patients with MSI constitute a rare group of immune checkpoint inhibitor (ICI)-responsive patients. Nonetheless, complete radiological responders comprise between 3% and 16% of MSI advanced CRC patients, which compares poorly with the 45% to 87% rate of pathological complete response in early MSI CRC patients treated with ICIs. In this review, we address the efficacy of current ICIs and the biological differences between early and advanced MSI CRC to potentially increase the efficacy of ICIs in both settings.

Mariam Rojas ... Joan Maurel

Published: February 18, 2025 Explor Dig Dis. 2025;4:100564
DOI: https://doi.org/10.37349/edd.2025.100564

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Microsatellite unstable (MSI) colorectal cancer (CRC) tumors have a high mutational load (particularly frame-shift mutations) that creates numerous neoantigens that are presented to major histocompatibility complex molecules and recognized by T cells. Consequently, MSI tumors have a higher presence of tumor-infiltrating lymphocytes than mismatch repair-proficient tumors. Colorectal cancer patients with MSI constitute a rare group of immune checkpoint inhibitor (ICI)-responsive patients. Nonetheless, complete radiological responders comprise between 3% and 16% of MSI advanced CRC patients, which compares poorly with the 45% to 87% rate of pathological complete response in early MSI CRC patients treated with ICIs. In this review, we address the efficacy of current ICIs and the biological differences between early and advanced MSI CRC to potentially increase the efficacy of ICIs in both settings.

Guest Editor

About the Special Issue

Call for Papers

Published Articles

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Methods:

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Methods:

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