Expression of Checkpoint Molecules in the Tumor Microenvironment of Intrahepatic Cholangiocarcinoma: Implications for Immune Checkpoint Blockade Therapy
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patient Recruitment
2.2. Sample Collection
2.3. Whole Slide Multiplexed Immunofluorescence (mIF)
2.4. Statistical Analysis
3. Results
3.1. Patient Characteristics and Clinical Data
3.2. Sclerotic Tumor Demonstrates Higher Expression of CD8 with PD-L1
3.3. Binary Logistic Regression for Nodal Status with Respect to Immune Cell Subsets
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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ICCA | ||
---|---|---|
Total | Percentage | |
Included patients | 50 | 100% |
Gender | ||
%Male | 24 | 48% |
%Female | 26 | 52% |
Median age (years) | 67 | |
Multifocal tumor | ||
%Yes | 17 | 34% |
%No | 33 | 66% |
Tumor stadium (T) | ||
%UICC T1 | 17 | 34% |
%UICC T2 | 24 | 48% |
%UICC T3 | 6 | 12% |
%UICC T4 | 3 | 6% |
Nodal status (N) | ||
%N0 | 32 | 64% |
%N1 + N2 | 16 | 32% |
%not known | 2 | 4% |
Tumor grading (G) | ||
%G1 | 0 | 0% |
%G2 | 37 | 74% |
%G3 | 10 | 20% |
%not known | 3 | 6% |
Perineural invasion (Pn) | ||
%Pn0 | 10 | 20% |
%Pn1 | 13 | 26% |
%not known | 27 | 54% |
Residual tumor (R) | ||
%R0 | 46 | 92% |
%R1 | 4 | 8% |
Lymphovascular invasion (L) | ||
%L0 | 38 | 76% |
%L1 | 9 | 18% |
%not known | 3 | 6% |
Median overall survival (months) | 32 |
iCCA-ROI | Number |
---|---|
Normal | 30 |
Tumor | 45 |
Interface | 30 |
Scleotic tumor | 32 |
Immune Cell Subset | Perihilar Cholangiocarcinoma | Intrahepatic Cholangiocarcinoma | ||
---|---|---|---|---|
OR (95%CI) | p-Value | OR (95%CI) | p-Value | |
Univariate analysis | ||||
Tumor_CD68 | 4.09 (1.16–14.43) | 0.028 | ||
Tumor_CD8_PD-L1_PD-L2 | 4.72 (1.07–20.89) | 0.041 | ||
Tumor_CD8_PD-L2 | 4.72 (1.07–20.89) | 0.041 | ||
Tumor_CD4_ICOS_TIGIT | 5.36 (1.25–23.04) | 0.024 | ||
Tumor_CD4_TIGIT | 6.11 (1.41–26.41) | 0.015 | ||
Tumor_CD8_ICOS_TIGIT | 6.11 (1.41–26.41) | 0.015 | ||
Tumor_CD8_ICOS_CTLA-4 | 6.11 (1.41–26.41) | 0.015 | ||
Liver_CD8_CTLA-4 | 0.13 (0.20–0.78) | 0.026 | ||
Liver_CD8_TIM3 | 0.13 (0.20–0.78) | 0.026 | ||
Multivariate analysis | ||||
Tumor_CD8_PD-L2 | 5.24 (1.01–27.18) | 0.048 | ||
Tumor_CD8_ICOS_TIGIT | 8.05 (1.60–40.53) | 0.011 |
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Heij, L.; Bednarsch, J.; Tan, X.; Rosin, M.; Appinger, S.; Reichel, K.; Pecina, D.; Doukas, M.; van Dam, R.M.; Garcia Vallejo, J.; et al. Expression of Checkpoint Molecules in the Tumor Microenvironment of Intrahepatic Cholangiocarcinoma: Implications for Immune Checkpoint Blockade Therapy. Cells 2023, 12, 851. https://doi.org/10.3390/cells12060851
Heij L, Bednarsch J, Tan X, Rosin M, Appinger S, Reichel K, Pecina D, Doukas M, van Dam RM, Garcia Vallejo J, et al. Expression of Checkpoint Molecules in the Tumor Microenvironment of Intrahepatic Cholangiocarcinoma: Implications for Immune Checkpoint Blockade Therapy. Cells. 2023; 12(6):851. https://doi.org/10.3390/cells12060851
Chicago/Turabian StyleHeij, Lara, Jan Bednarsch, Xiuxiang Tan, Mika Rosin, Simone Appinger, Konrad Reichel, Dana Pecina, Michail Doukas, Ronald M. van Dam, Juan Garcia Vallejo, and et al. 2023. "Expression of Checkpoint Molecules in the Tumor Microenvironment of Intrahepatic Cholangiocarcinoma: Implications for Immune Checkpoint Blockade Therapy" Cells 12, no. 6: 851. https://doi.org/10.3390/cells12060851