Immunotherapy Strategies for Gastric Cancer Management

Gastric cancer remains a major global health challenge due to late diagnosis and limited efficacy of conventional therapies. Immunotherapy has emerged as a transformative modality, seeking to harness host immunity to eradicate malignant cells. Strategies centre on immune checkpoint blockade, adoptive cell transfer, cancer vaccines and combination regimens with targeted agents or chemotherapy. Checkpoint inhibitors directed against programmed cell death-1 (PD-1) and its ligand (PD-L1) have yielded durable responses in subgroups of patients, particularly those exhibiting high microsatellite instability, elevated tumour mutational burden or specific molecular subtypes such as Epstein–Barr virus-positive tumours. Novel approaches now exploit multi-modal data integration and refined biomarkers to predict response, while adoptive transfer of engineered lymphocytes and tumour microenvironment modulation are under clinical evaluation. Emphasis has shifted towards personalised immunotherapy, guided by spatial and phenotypic profiling of tumour-infiltrating immune cells and machine-learning algorithms. Together, these advances promise to redefine management algorithms for gastric cancer, with real-world applications in patient selection, treatment optimisation and long-term surveillance.

Research from Nature Portfolio

Recent studies have refined predictive biomarkers by dissecting the tumour immune microenvironment at sub-cellular resolution. A multidimensional signature combining densities of distinct T-cell and macrophage subsets as well as their spatial relationships was established using multiplex immunohistochemistry. This signature reliably identifies patients most likely to benefit from anti-PD-1/PD-L1 therapy and correlates with survival outcomes. By quantifying the interplay between immune effectors and inhibitory signals in situ, this approach offers a precise tool for patient stratification beyond conventional single-biomarker assays.

Immunotherapy Strategies for Gastric Cancer Management publication trend

The graph below shows the total number of articles in immunotherapy strategies for gastric cancer management across all publications each year (not limited to Nature Index journals).

Technical terms

PD-1: A receptor on T lymphocytes that downregulates immune activity upon binding its ligands.

PD-L1: A ligand expressed on tumour or immune cells that interacts with PD-1 to inhibit T-cell function.

HER2: A growth factor receptor overexpressed in a subset of gastric cancers, targetable by monoclonal antibodies.

Tumour microenvironment (TME): The cellular and molecular milieu surrounding tumour cells, including immune, stromal and vascular components.

Tumour mutational burden (TMB): The total number of somatic mutations per coding area of a tumour genome, associated with neoantigen load.

Microsatellite instability (MSI): A form of genetic hypermutability resulting from defective DNA mismatch repair mechanisms.

Combined positive score (CPS): A metric calculating PD-L1 expression on tumour and immune cells relative to total viable cells.

References

1. Predicting gastric cancer response to anti-HER2 therapy or anti-HER2 combined immunotherapy based on multi-modal data. Signal Transduction and Targeted Therapy (2024).
2. Clinicopathological and molecular features of responders to nivolumab for patients with advanced gastric cancer. Journal for ImmunoTherapy of Cancer (2019).
3. Predicting response to immunotherapy in gastric cancer via multi-dimensional analyses of the tumour immune microenvironment. Nature Communications (2022).
4. Pembrolizumab versus paclitaxel for previously treated PD-L1-positive advanced gastric or gastroesophageal junction cancer: 2-year update of the randomized phase 3 KEYNOTE-061 trial. Gastric Cancer (2021).
5. The New Era of Immunotherapy in Gastric Cancer. Cancers (2022).