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Updated: Jan 12, 2026
Enrichment and Characterization of the Tumor Immune and Non-immune Microenvironments in Established Subcutaneous Murine Tumors
Published on: June 7, 2018
Single-cell profiling unveils the immuno-favorable tumor microenvironment remodeling after successful neoadjuvant
Qiu-Yi Tang1,2,3,4, Yi-Jian Zhang1,2,3,4, Zi-You Wu5
1Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Background:
Neoadjuvant treatment has demonstrated clinical benefits in advanced gallbladder cancer (GBC). However, the overall response rate remains suboptimal, and the underlying mechanisms driving treatment efficacy are not fully understood.
Materials And Methods:
This study aimed to evaluate the therapeutic effects of neoadjuvant chemo-immunotherapy (NAT) combining gemcitabine, nab-paclitaxel, and anti-PD-1 immunotherapy in advanced GBC, and to investigate the associated tumor microenvironment (TME) alterations. Single-cell RNA sequencing and multiplex immunohistochemistry were utilized to analyze the cellular composition of the TME in patients who successfully underwent downstaging.
Results:
NAT significantly reshaped the tumor-immune landscape, characterized by an expansion of follicular helper T (Tfh) cells and the formation of tertiary lymphoid structures (TLSs) in 50% of treated tumors. Inflammatory cancer-associated fibroblasts (CAFs) increased and exhibited upregulation of CCL19 and CXCL12 , potentially promoting Tfh cell recruitment and TLS formation. Additionally, NAT led to an expansion of GZMB + cytotoxic CD8 + T cells with an exhausted phenotype in GBC, but not in adjacent normal tissues. The treatment also increased the number and effector functions of natural killer cells while reducing tumor-promoting macrophages and angiogenesis-related CAFs. Furthermore, NAT decreased the cancer stem cell-like subpopulation while increasing a cancer cell subset with enhanced antigen-presenting capacity.
Conclusion:
This study suggested the potential efficacy of NAT in advanced GBC and revealed alterations in the TME following treatment. The findings provided insights into the mechanisms underlying NAT responses and offered valuable directions for optimizing therapeutic strategies in GBC.
Insights
Neoadjuvant chemo-immunotherapy (NAT) shows promise for advanced gallbladder cancer (GBC) by reshaping the tumor microenvironment (TME). This treatment expands beneficial immune cells and reduces tumor-promoting elements, offering new therapeutic strategies.
Area of Science:
- Oncology
- Immunology
- Cancer Research
Background:
- Neoadjuvant treatment offers clinical benefits for advanced gallbladder cancer (GBC), but suboptimal response rates and unclear mechanisms necessitate further investigation.
- Understanding the tumor microenvironment (TME) is crucial for improving treatment efficacy in GBC.
Purpose of the Study:
- To evaluate the therapeutic effects of neoadjuvant chemo-immunotherapy (NAT) combining gemcitabine, nab-paclitaxel, and anti-PD-1 immunotherapy in advanced GBC.
- To investigate the associated tumor microenvironment (TME) alterations following NAT in GBC patients.
Main Methods:
- Single-cell RNA sequencing and multiplex immunohistochemistry were used to analyze TME cellular composition.
- Patient samples from those who successfully underwent downstaging after NAT were analyzed.
Main Results:
- NAT significantly altered the tumor-immune landscape, expanding follicular helper T (Tfh) cells and forming tertiary lymphoid structures (TLSs) in 50% of tumors.
- Increased inflammatory cancer-associated fibroblasts (CAFs) potentially recruit Tfh cells and promote TLS formation.
- NAT expanded cytotoxic CD8+ T cells and natural killer cells, reduced tumor-promoting macrophages and CAFs, decreased cancer stem cells, and enhanced cancer cell antigen presentation.
Conclusions:
- Neoadjuvant chemo-immunotherapy (NAT) demonstrates potential efficacy in advanced GBC by modulating the TME.
- Findings offer insights into NAT mechanisms and guide optimization of GBC therapeutic strategies.
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