Related Experiment Video
Updated: Feb 2, 2026
Optimized Interferon-gamma ELISpot Assay to Measure T Cell Responses in the Guinea Pig Model after Vaccination
Published on: January 20, 2019
Hyperresponsiveness to interferon gamma exposure as a response mechanism to anti-PD-1 therapy in microsatellite
Wenli Yuan1, Deyao Deng1, Hongchao Jiang2
1Department of Clinical Laboratory, The Fourth Affiliated Hospital of Kunming Medical University, Kunming, 650021, People's Republic of China.
Abstract:
Colorectal cancer (CRC) with high-level microsatellite instability (MSI-H) tends to be associated with a better response to programmed death receptor-1 (PD-1) blockade than does microsatellite stable CRC. However, emerging evidence makes the use of programmed death ligand-1 (PD-L1) as a biomarker problematic. Here, we sought to characterize the interactions between PD-L1 expression and the response to PD-1 blockade therapy in BALB/c mice with a subcutaneous tumor challenge. We further focused on interferon gamma (IFNγ)-induced PD-L1 expression in an in vitro setting to evaluate the responsiveness to IFNγ exposure and the specific signaling of PD-1 in HCT116 and SW480 cell lines. In this study, enhanced PD-L1 expression increased survival in CT26 cells, and PD-1 blockade increased the CTL profile and apoptotic cells in mice with CRC. Our in vitro findings showed that PD-L1 expression was significantly upregulated by a low-dose IFNγ treatment, and the MSI-H cell line might exhibit hyperresponsiveness to IFNγ exposure partly through the JAK-STAT pathway. These results suggest that intrinsic PD-L1 in cooperation with extrinsic IFNγ exposure in CRC may be more responsive to anti-PD-1 therapy, mainly through the CTL profile in the tumor microenvironment.
Insights
High microsatellite instability (MSI-H) colorectal cancer (CRC) shows promise with PD-1 blockade. Interferon gamma (IFNγ) boosts PD-L1 expression, enhancing anti-PD-1 therapy response in MSI-H CRC via the JAK-STAT pathway.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Colorectal cancer (CRC) with high-level microsatellite instability (MSI-H) generally responds better to programmed death receptor-1 (PD-1) blockade compared to microsatellite-stable CRC.
- The utility of programmed death ligand-1 (PD-L1) as a predictive biomarker for PD-1 blockade therapy is increasingly debated.
- Understanding the interplay between PD-L1 expression and therapeutic response is crucial for optimizing cancer immunotherapy.
Purpose of the Study:
- To investigate the relationship between PD-L1 expression and the efficacy of PD-1 blockade in a murine model of CRC.
- To characterize the in vitro induction of PD-L1 by interferon gamma (IFNγ) and its signaling pathways in CRC cell lines.
- To evaluate the combined effect of intrinsic PD-L1 and IFNγ exposure on anti-PD-1 therapy response.
Main Methods:
- Utilized a subcutaneous tumor challenge model in BALB/c mice with colorectal cancer (CT26 cells).
- Assessed PD-1 blockade efficacy by monitoring survival, cytotoxic T lymphocyte (CTL) profile, and apoptosis.
- Conducted in vitro experiments using HCT116 and SW480 cell lines to study IFNγ-induced PD-L1 expression and JAK-STAT pathway activation.
Main Results:
- Enhanced PD-L1 expression in CT26 cells correlated with increased survival in mice treated with PD-1 blockade.
- PD-1 blockade therapy led to an increased CTL profile and elevated levels of apoptotic cells in CRC-bearing mice.
- In vitro, low-dose IFNγ significantly upregulated PD-L1 expression, with MSI-H cell lines showing potential hyperresponsiveness via the JAK-STAT pathway.
Conclusions:
- Intrinsic PD-L1 expression, particularly when combined with extrinsic IFNγ stimulation, may enhance responsiveness to anti-PD-1 therapy in MSI-H colorectal cancer.
- The CTL profile within the tumor microenvironment appears to be a key mechanism mediating the therapeutic benefits.
- These findings suggest a synergistic approach involving IFNγ and PD-1 blockade could be beneficial for specific CRC patient populations.
More Related Videos
07:43Using 22C3 Anti-PD-L1 Antibody Concentrate on Biopsy and Cytology Samples from Non-small Cell Lung Cancer Patients
Published on: September 25, 2018
07:20Ex vivo Expansion of Tumor-reactive T Cells by Means of Bryostatin 1/Ionomycin and the Common Gamma Chain Cytokines Formulation
Published on: January 14, 2011
Related Concept Videos
02:25SN1 Reaction: Mechanism
Firstly, the haloalkane ionizes to generate a carbocation intermediate and a halide ion. This heterolytic cleavage is highly endothermic with large activation energy. The ionization of the substrate, facilitated by a...
02:49Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
01:17Radical Anti-Markovnikov Addition to Alkenes: Mechanism
The mechanism starts with chain initiation, which involves two steps. In the first chain initiation step, a weak peroxide bond is homolytically cleaved upon mild heating to form two alkoxy radicals. In the second initiation step, a hydrogen atom is abstracted by the alkoxy...
02:17Microtubule Instability