Immune Heterogeneity Between Primary Tumors and Corresponding Metastatic Lesions and Response to Platinum Therapy in Primary Ovarian Cancer
Abstract
:1. Introduction
2. Results
2.1. Patient Characteristics
2.2. Immune Infiltrate in Primary Tumor
2.3. Immune Infiltrate in Metastatic Lesions
2.4. Associations of Immune Heterogeneity
3. Discussion
4. Patients and Methods
4.1. Study Population
4.2. Immunohistochemistry
4.3. Semiquantitative Analysis of the CD45+ Infiltrate
4.4. Quantitative Analysis of Immune Cells
4.5. Semiquantitative Analysis of PD-L1
4.6. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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n or Value | % | ||
---|---|---|---|
Age | mean/median | 62/66 years | |
range | 24–83 years | ||
FIGO Stage | I/II | 0 | 0.0 |
III | 35 | 71.4 | |
IV | 14 | 28.6 | |
pT | pT2 | 5 | 10.2 |
pT3 | 44 | 89.8 | |
pN | pN0 | 6 | 12.2 |
pN1 | 32 | 65.3 | |
Nx | 11 | 22.4 | |
cM | cM0 | 35 | 71.4 |
cM1 | 14 | 28.6 | |
Primary Tumor Site | Ovarian | 39 | 79.6 |
Fallopian Tube | 7 | 14.3 | |
Peritoneal | 3 | 6.1 | |
Histological Subtype | Serous | 44 | 89.8 |
Other | 5 | 10.2 | |
Grading | G1/G2 | 1 | 4.0 |
G3 | 47 | 95.9 | |
Ascites | yes | 41 | 83.7 |
no | 8 | 16.3 | |
Macroscopic Residual Tumor after Surgery | None | 35 | 71.4 |
<1 cm | 8 | 16.3 | |
>1 cm | 6 | 12.2 | |
Lymphatic Vessel Invasion | yes | 26 | 53.1 |
no | 21 | 42.9 | |
missing | 2 | 4.1 | |
Vascular Invasion | yes | 9 | 18.4 |
no | 38 | 77.6 | |
missing | 2 | 4.1 | |
First-Line-Treatment | C | 5 | 10.2 |
C+P | 15 | 30.6 | |
C+P+B | 25 | 51.0 | |
None | 4 | 8.2 | |
Relapse after Chemotherapy | < 6 months | 2 | 4.1 |
6–12 months | 12 | 24.5 | |
>12 months | 28 | 57.1 | |
none or non-sufficient chemotherapy | 7 | 14.3 |
PT | OM | PE | ||
---|---|---|---|---|
Rating | CD45 stromal | |||
Mode (Range) | 3 (1–5) | 3 (2–5) | 3;4 (2–5) | |
CD45 intratumoral | ||||
Mode (Range) | 1 (0–3) | 1 (0–3) | 1 (0–3) | |
Cell Count | CD3 stromal | |||
Mean (Range) | 626 (5–2491) | 1241 (202–4157) | 851 (117–2766) | |
CD3 intratumoral | ||||
Mean (Range) | 201 (0–1134) | 212 (0–569) | 272 (0–985) | |
CD8 stromal | ||||
Mean (Range) | 318 (0–1049) | 623 (83–1910) | 364 (0–843) | |
CD8 intratumoral | ||||
Mean (Range) | 88 (0–716) | 104 (0–636) | 130 (0–494) | |
PD-1 stromal | ||||
Mean (Range) | 73 (0–404) | 91 (0–335) | 130 (0–601) | |
PD-1 intratumoral | ||||
Mean (Range) | 26 (0–191) | 21 (0–83) | 33 (0–145) | |
Expression | PD-L1 | |||
Median (Range) | 1% (0–20%) | 0.5% (0–20%) | 3% (0–20%) |
PT | OM/PT | PE/PT | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Platinum-Sensitivity * | Platinum-Sensitivity * | Platinum-Sensitivity * | |||||||||||||
n | Red | Full | p# | n | Red | Full | p# | n | Red | Full | p# | ||||
CD45 stromal | 42 | 1 | 19 | 0.350 | 12 | 0.250 | |||||||||
Low | 4 | 8 | OM ≤ PT | 2 | 7 | PE ≤ PT | 2 | 9 | |||||||
High | 10 | 20 | OM > PT | 5 | 5 | PE > PT | 1 | 0 | |||||||
CD45 intratumoral | 42 | 1 | 19 | 1 | 12 | 1 | |||||||||
Low | 8 | 15 | OM ≤ PT | 6 | 11 | PE ≤ PT | 3 | 8 | |||||||
High | 6 | 13 | OM > PT | 1 | 1 | PE > PT | 0 | 1 | |||||||
CD3 stromal | 42 | 1 | 19 | 1 | 12 | 0.523 | |||||||||
Low | 8 | 16 | OM ≤ PT | 1 | 3 | PE ≤ PT | 2 | 3 | |||||||
High | 6 | 12 | OM > PT | 6 | 9 | PE > PT | 1 | 6 | |||||||
CD3 intratumoral | 42 | 0.057 | 19 | 0.633 | 12 | 1 | |||||||||
Low | 11 | 13 | OM ≤ PT | 2 | 6 | PE ≤ PT | 2 | 4 | |||||||
High | 3 | 15 | OM > PT | 5 | 6 | PE > PT | 1 | 5 | |||||||
CD8 stromal | 42 | 0.748 | 19 | 1 | 12 | 0.523 | |||||||||
Low | 7 | 16 | OM ≤ PT | 2 | 3 | PE ≤ PT | 1 | 6 | |||||||
High | 7 | 12 | OM > PT | 5 | 9 | PE > PT | 2 | 3 | |||||||
CD8 intratumoral | 42 | 1 | 19 | 0.656 | 12 | 0.045 | |||||||||
Low | 9 | 18 | OM ≤ PT | 2 | 5 | PE ≤ PT | 3 | 2 | |||||||
High | 5 | 10 | OM > PT | 5 | 7 | PE > PT | 0 | 7 | |||||||
PD-1 stromal | 42 | 0.283 | 19 | 1 | 12 | 0.045 | |||||||||
Low | 12 | 19 | OM ≤ PT | 2 | 4 | PE ≤ PT | 0 | 7 | |||||||
High | 2 | 9 | OM > PT | 5 | 8 | PE > PT | 3 | 2 | |||||||
PD-1 intratumoral | 42 | 0.738 | 19 | 1 | 12 | 1 | |||||||||
Low | 10 | 18 | OM ≤ PT | 5 | 8 | PE ≤ PT | 3 | 7 | |||||||
High | 4 | 10 | OM > PT | 2 | 4 | PE > PT | 0 | 2 | |||||||
PD-L1 Positivity | 42 | 1 | 19 | 0.603 | 12 | 1 | |||||||||
No | 5 | 10 | OM ≤ PT | 5 | 10 | PE ≤ PT | 2 | 7 | |||||||
Yes | 9 | 18 | OM > PT | 2 | 2 | PE > PT | 1 | 2 |
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Dötzer, K.; Schlüter, F.; Schoenberg, M.B.; Bazhin, A.V.; Edler von Koch, F.; Schnelzer, A.; Anthuber, S.; Grab, D.; Czogalla, B.; Burges, A.; et al. Immune Heterogeneity Between Primary Tumors and Corresponding Metastatic Lesions and Response to Platinum Therapy in Primary Ovarian Cancer. Cancers 2019, 11, 1250. https://doi.org/10.3390/cancers11091250
Dötzer K, Schlüter F, Schoenberg MB, Bazhin AV, Edler von Koch F, Schnelzer A, Anthuber S, Grab D, Czogalla B, Burges A, et al. Immune Heterogeneity Between Primary Tumors and Corresponding Metastatic Lesions and Response to Platinum Therapy in Primary Ovarian Cancer. Cancers. 2019; 11(9):1250. https://doi.org/10.3390/cancers11091250
Chicago/Turabian StyleDötzer, Katharina, Friederike Schlüter, Markus Bo Schoenberg, Alexandr V. Bazhin, Franz Edler von Koch, Andreas Schnelzer, Sabine Anthuber, Dieter Grab, Bastian Czogalla, Alexander Burges, and et al. 2019. "Immune Heterogeneity Between Primary Tumors and Corresponding Metastatic Lesions and Response to Platinum Therapy in Primary Ovarian Cancer" Cancers 11, no. 9: 1250. https://doi.org/10.3390/cancers11091250