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PD-1/PD-L blockade in gastrointestinal cancers: lessons learned and the road toward precision immunotherapy
Junyu Long1, Jianzhen Lin1, Anqiang Wang1
1Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Abstract:
Gastrointestinal (GI) malignancies are the most prevalent tumors worldwide, with increasing incidence and mortality. Although surgical resection, chemotherapy, radiotherapy, and molecular targeted therapy have led to significant advances in the treatment of GI cancer patients, overall survival is still low. Therefore, alternative strategies must be identified to improve patient outcomes. In the tumor microenvironment, tumor cells can escape the host immune response through the interaction of PD-1 and PD-L, which inhibits the function of T cells and tumor-infiltrating lymphocytes while increasing the function of immunosuppressive T regulatory cells. The use of an anti-PD-1/PD-L blockade enables reprogramming of the immune system to efficiently identify and kill tumor cells. In recent years, the efficacy of PD-1/PD-L blockade has been demonstrated in many tumors, and this treatment is expected to be a pan-immunotherapy for tumors. Here, we review the signaling pathway underlying the dysregulation of PD-1/PD-L in tumors, summarize the current clinical data for PD-1/PD-L inhibitors in GI malignancies, and discuss road toward precision immunotherapy in relation to PD-1/PD-L blockade. The preliminary data for PD-1/PD-L inhibitors are encouraging, and the precision immunotherapy of PD-1/PD-L inhibitors will be a viable and pivotal clinical strategy for GI cancer therapy.
Insights
Programmed cell death protein 1 (PD-1) and its ligand (PD-L) blockade shows promise for gastrointestinal (GI) cancer. This immunotherapy strategy reprograms the immune system to fight GI malignancies, offering a potential new treatment avenue.
Area of Science:
- Oncology
- Immunology
- Gastroenterology
Background:
- Gastrointestinal (GI) malignancies represent a significant global health burden with high mortality rates.
- Current treatments like surgery, chemotherapy, and targeted therapy offer limited survival benefits for many GI cancer patients.
- Tumor cells evade immune surveillance via the PD-1/PD-L pathway, suppressing anti-tumor immune responses.
Purpose of the Study:
- To review the PD-1/PD-L signaling pathway in tumors.
- To summarize clinical data on PD-1/PD-L inhibitors in GI malignancies.
- To discuss the future of precision immunotherapy using PD-1/PD-L blockade for GI cancers.
Main Methods:
- Literature review of PD-1/PD-L signaling in cancer.
- Analysis of current clinical trial data for PD-1/PD-L inhibitors in GI cancers.
- Discussion of precision immunotherapy strategies.
Main Results:
- PD-1/PD-L interaction inhibits T cell function and promotes immunosuppression in the tumor microenvironment.
- PD-1/PD-L blockade demonstrates efficacy in various tumors, suggesting potential as a pan-immunotherapy.
- Preliminary clinical data for PD-1/PD-L inhibitors in GI malignancies are encouraging.
Conclusions:
- PD-1/PD-L blockade offers a promising strategy to overcome immune evasion in GI cancers.
- Precision immunotherapy targeting the PD-1/PD-L pathway is a viable and pivotal approach for GI cancer treatment.
- Further research and clinical application of PD-1/PD-L inhibitors are warranted for improved patient outcomes.
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