PD-L1 Induction by Cancer-Associated Fibroblast-Derived Factors in Lung Adenocarcinoma Cells
Abstract
:1. Introduction
2. Results
2.1. α-SMA Status in Stromal Area of Lung Cancer Was Significantly Associated with PD-L1 Status in Carcinoma Cells and Adverse Clinical Outcome of the Patients
2.2. Conditioned Medium of CAFs Significantly Increased PD-L1 Expression at Both mRNA and Protein Levels
2.3. Profiles of Cytokines Secreted from CAFs Were Altered by Co-Culture with Adenocarcinoma Cells
2.4. CXCL2 Increased PD-L1 mRNA in Adenocarcinoma Cells
3. Discussion
4. Materials and Methods
4.1. Patients
4.2. Immunohistochemistry
4.3. Cell Lines
4.4. Immunocytochemistry
4.5. Conditioned Medium
4.6. Quantitative RT-PCR
4.7. Capillary Electrophoresis Immunoassay
4.8. Co-Culture System
4.9. Cytokine Analysis
4.10. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Total | α-SMA | α-SMA | p-Value | ||
---|---|---|---|---|---|
High | Low | ||||
Age | median | 64 | 63 | 64 | 0.9803 |
(years) | max | 80 | 80 | 74 | |
min | 34 | 34 | 46 | ||
Sex | male | 8 | 6 | 2 | |
female | 19 | 10 | 9 | ||
Smoking | smoker | 6 | 5 | 1 | 0.3497 |
never | 21 | 11 | 10 | ||
Brinkman index | median | 0† | 0† | 0† | 0.1646 |
max | 1200 | 1200 | 700 | ||
min | 0 | 0 | 0 | ||
Size of tumor | median | 28 | 27 | 30.5 | 0.9069 |
(mm) | max | 80 | 80 | 40 | |
min | 13 | 15 | 13 | ||
EGFR | exon 19 del | 12 | 3 | 9 | 0.3172 |
mutation | exon 21 L858R | 11 | 6 | 5 | |
G719X, S768I | 1 | 1 | 0 | ||
ex20 Ins | 1 | 0 | 1 | ||
unknown | 2 | 1 | 1 | ||
Response to | CR | 1 | 1 | 0 | 0.7354 |
EGFR-TKI | PR | 17 | 10 | 7 | |
SD | 8 | 4 | 4 | ||
PD | 1 | 1 | 0 | ||
Ki-67 LI of carcinoma cells (%) | median | 12.3 | 13.1 | 10.9 | 0.5053 |
max | 58.8 | 58.8 | 32 | ||
min | 3.3 | 3.3 | 4.7 | ||
pStage | I | 9 | 2 | 7 | 0.0263* |
II | 5 | 4 | 1 | ||
III | 10 | 8 | 2 | ||
IV | 3 | 2 | 1 | ||
pT | 1 | 13 | 7 | 6 | 0.6146 |
2 | 11 | 7 | 4 | ||
3 | 1 | 1 | 0 | ||
4 | 2 | 1 | 1 | ||
pN | 0 | 13 | 5 | 8 | 0.0514# |
1 | 5 | 4 | 1 | ||
2 | 9 | 7 | 2 | ||
3 | 0 | 0 | 0 | ||
cM | 0 | 24 | 14 | 10 | 1.000 |
1 | 3 | 2 | 1 | ||
PD-L1 | positive | 5 | 5 | 0 | 0.0598# |
negative | 22 | 11 | 11 | ||
CD3 | median | 766 | 758 | 767 | 0.941 |
max | 1656 | 1656 | 1022 | ||
min | 404 | 404 | 462 | ||
CD4 | median | 697 | 693.5 | 697 | 0.2669 |
max | 1486 | 1486 | 806 | ||
min | 263 | 303 | 263 | ||
CD8 | median | 416 | 432.5 | 399 | 0.7484 |
max | 611 | 599 | 611 | ||
min | 177 | 209 | 177 | ||
Foxp3 | median | 518 | 110.5 | 111 | 0.9214 |
max | 111 | 518 | 249 | ||
min | 15 | 32 | 15 | ||
Foxp3/CD8 | median | 0.3 | 0.28 | 0.31 | 0.941 |
max | 1 | 1 | 0.89 | ||
min | 0.03 | 0.12 | 0.03 | ||
CD8/CD4 | median | 0.67 | 0.61 | 0.7 | 0.4443 |
max | 1.3 | 1.03 | 1.3 | ||
min | 0.26 | 0.33 | 0.26 |
Total | α-SMA | α-SMA | p-Value | ||
---|---|---|---|---|---|
High | Low | ||||
Age | median | 66 | 64.5 | 70 | 0.0872 |
(years) | max | 82 | 80 | 82 | |
min | 30 | 30 | 46 | ||
Sex | male | 58 | 37 | 21 | 0.0241* |
female | 55 | 23 | 32 | ||
Smoking | smoker | 61 | 38 | 23 | 0.0391* |
never | 52 | 22 | 30 | ||
Brinkman index | median | 240 | 520 | 0† | 0.0131* |
max | 1920 | 1840 | 1920 | ||
min | 0 | 0 | 0 | ||
Size of tumor | median | 25 | 24.5 | 27 | 0.2570 |
(mm) | max | 80 | 80 | 70 | |
min | 10 | 10 | 10 | ||
pStage | I | 68 | 29 | 39 | 0.0022* |
II | 13 | 7 | 6 | ||
III | 24 | 17 | 7 | ||
IV | 8 | 7 | 1 | ||
pT | 1 | 65 | 34 | 31 | 0.7978 |
2 | 36 | 19 | 17 | ||
3 | 3 | 2 | 1 | ||
4 | 9 | 5 | 4 | ||
pN | 0 | 85 | 38 | 47 | 0.0015* |
1 | 8 | 6 | 2 | ||
2 | 19 | 15 | 4 | ||
3 | 1 | 1 | 0 | ||
cM | 0 | 105 | 53 | 52 | 0.0648# |
1 | 8 | 7 | 1 | ||
PD-L1 | positive | 17 | 17 | 0 | <0.0001* |
negative | 96 | 43 | 53 |
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Inoue, C.; Miki, Y.; Saito, R.; Hata, S.; Abe, J.; Sato, I.; Okada, Y.; Sasano, H. PD-L1 Induction by Cancer-Associated Fibroblast-Derived Factors in Lung Adenocarcinoma Cells. Cancers 2019, 11, 1257. https://doi.org/10.3390/cancers11091257
Inoue C, Miki Y, Saito R, Hata S, Abe J, Sato I, Okada Y, Sasano H. PD-L1 Induction by Cancer-Associated Fibroblast-Derived Factors in Lung Adenocarcinoma Cells. Cancers. 2019; 11(9):1257. https://doi.org/10.3390/cancers11091257
Chicago/Turabian StyleInoue, Chihiro, Yasuhiro Miki, Ryoko Saito, Shuko Hata, Jiro Abe, Ikuro Sato, Yoshinori Okada, and Hironobu Sasano. 2019. "PD-L1 Induction by Cancer-Associated Fibroblast-Derived Factors in Lung Adenocarcinoma Cells" Cancers 11, no. 9: 1257. https://doi.org/10.3390/cancers11091257