Immunotherapy Approaches in Gastroesophageal Cancer

Gastroesophageal cancers, encompassing both gastric and oesophageal malignancies, have traditionally carried a poor prognosis despite advances in surgery and chemotherapy. Over the past decade, the advent of immunotherapy—particularly immune checkpoint blockade—has transformed treatment paradigms. Antibodies targeting programmed cell death-1 (PD-1) and its ligand PD-L1 restore anti-tumour T-cell activity, while inhibitors of cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) further potentiate immune responses. Integration of these agents with cytotoxic chemotherapy in first-line settings has prolonged overall survival and progression-free survival, especially in patients whose tumours express higher PD-L1 combined positive scores. In later lines, monotherapy with checkpoint inhibitors offers an option for those refractory to standard regimens, with durable responses seen in a minority. Ongoing work seeks to refine patient selection through biomarkers such as tumour mutational burden and immune-cell infiltrates, to explore combinations with HER2-directed therapy and to develop novel modalities including therapeutic vaccines and adoptive cell transfer. Together, these strategies underscore a global shift towards precision immunotherapy in gastroesophageal cancer, offering new avenues for durable control of this challenging disease.

Research from Nature Portfolio

Long-term results from a pivotal randomised trial comparing first-line chemotherapy with or without a PD-1 inhibitor demonstrate sustained survival benefit at two years. Patients receiving the combination exhibited a hazard ratio for death of approximately 0.70 in PD-L1-positive tumours and 0.79 in the overall population, with no new safety concerns. A parallel comparison of dual checkpoint blockade against chemotherapy showed promising activity but did not reach prespecified significance thresholds, reinforcing the current standard of combining PD-1 blockade with cytotoxic agents in advanced gastroesophageal adenocarcinoma.

Immunotherapy Approaches in Gastroesophageal Cancer publication trend

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

Technical terms

Immune checkpoint inhibitor: A monoclonal antibody that blocks regulatory pathways in T cells (e.g. PD-1, PD-L1, CTLA-4) to enhance anti-tumour immunity.

PD-L1 combined positive score (CPS): The ratio of PD-L1-positive tumour and immune cells to total viable tumour cells, expressed as a percentage, used to stratify patients for immunotherapy.

Tumour mutational burden (TMB): The total number of somatic mutations per coding area of a tumour genome, serving as a biomarker for likelihood of response to immunotherapy.

Single-cell RNA-sequencing: A technique to profile gene expression at the individual cell level, enabling detailed characterisation of tumour and immune cell populations.

Tumour monocyte content: The proportion of monocyte lineage cells within the tumour microenvironment, which can influence response to combined immunotherapy and chemotherapy.

References

1. Nivolumab plus chemotherapy or ipilimumab in gastro-oesophageal cancer. Nature (2022).
2. Tumor monocyte content predicts immunochemotherapy outcomes in esophageal adenocarcinoma. Cancer Cell (2023).
3. FOLFIRI Plus Durvalumab With or Without Tremelimumab in Second-Line Treatment of Advanced Gastric or Gastroesophageal Junction Adenocarcinoma. JAMA Oncology (2024).