Innate Immune Cells in the Tumor Microenvironment of Liver Metastasis from Colorectal Cancer: Contribution to a Comprehensive Therapy
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Participants and Sample Collection
2.2. Histological Analysis
2.3. Flow Cytometry Characterization of Innate Immune Cells
2.3.1. Staining Protocol
2.3.2. Sample Acquisition and Analysis
3. Results
3.1. Innate Immune Cells in Liver Colorectal Cancer Metastasis Microenvironment
3.2. Mean Fluorescence Intensity (MFI) Analysis of CD206 and CD274 Reveals Differential Expression on Cells from CRC Liver Metastasis
3.3. Blood Sample Analysis of CRCLM Patients
3.4. The Percentage of CD206+ and CD274+ Monocytes Influences the Disease-Free Survival Time of CRCLM Patients
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Variable | (n = 47) |
---|---|
Age at surgical resection | |
Mean ± SD; range | 59.1 ± 12.8; 36–90 |
Variable | Number (%) |
Gender | |
Male | 31 (66) |
Female | 16 (34) |
Presentation | |
Synchronous | 26 (55) |
Metachronous | 21 (45) |
Primary tumor location | |
Sigmoid | 16 (34) |
Ascending | 10 (21) |
Descending | 5 (11) |
Splenic Flexure | 4 (9) |
Hepatic Flexure | 1 (2) |
Transverse | 2 (4) |
Rectal | 9 (19) |
T stage of the primary colorectal tumor | |
3 | 33 (70) |
4a | 12 (26) |
4b | 2 (4) |
First approach | |
Liver First | 6 (13) |
Colectomy | 34 (72) |
Synchronous resection | 7 (15) |
Preoperative systemic chemotherapy | 27 (57) |
Variable | (n = 47) |
Number of colorectal liver metastases | |
Mean ± SD; range | 2.3 ± 1.8; 1–10 |
Size of the largest colorectal liver metastases (cm) | |
Mean ± SD; range | 3.8 ± 2.4; 0.4–12 |
Variable | Number (%) |
Histologic growth pattern | |
Desmoplastic | 17 (36) |
Non-desmoplastic | 30 (64) |
Status | |
Dead | 3 (6) |
Alive | 44 (94) |
Fluorochromes | ||||||||
---|---|---|---|---|---|---|---|---|
Tube | PB | PO | FITC | PE | PerCP-Cy5.5 | PE-Cy7 | APC | APC-H7 |
1 | CD274 Biolegend (29E.2A3) (5 µL) | CD45 BD Biosciences (2D1) (2.5 µL) | Cito18 Cytognos (Ks18.04) (2.5 µL) | EpCAM BD Biosciences (EBA-1) (10 µL) | CD206 Biolegend (15–2) (5 µL) | CD16 BD Pharmingen (3G8) (2 µL) | CD33 BD Biosciences (P67.6) (2.5 µL) | CD14 BD Biosciences (mφp9) (2.5 µL) |
Cell Types | Non-Tumor (%) ± SEM | Tumor (%) ± SEM | p Value | Tumor | p Value | |
---|---|---|---|---|---|---|
Non-Desmoplastic (%) ± SEM | Desmoplastic (%) ± SEM | |||||
Eosinophils | 0.53 ± 0.17 | 0.01 ± 0.01 | 0.0001 a | 0.002 ± 0.002 | 0.02 ± 0.01 | 0.38 |
Eosinophils (after removing non-hematopoietic cells) | 0.81 ± 0.26 | 0.04 ± 0.03 | 0.0001 a | 0.01 ± 0.01 | 0.11 ± 0.08 | 0.38 |
Neutrophils | 22.50 ± 2.50 | 6.87 ± 1.56 | <0.0001 b | 5.63 ± 1.57 | 4.20 ± 1.59 | 0.38 |
Neutrophils (after removing non-hematopoietic cells) | 34.88 ± 3.88 | 32.66 ± 7.43 | 0.50 | 27.65 ± 7.71 | 24.03 ± 9.05 | 0.64 |
Lymphocytes | 31.36 ± 2.93 | 11.87 ± 1.99 | <0.0001 b | 12.17 ± 1.62 | 11.96 ± 4.30 | 0.44 |
Lymphocytes (after removing non-hematopoietic cells) | 48.61 ± 4.53 | 56.44 ± 9.44 | 0.79 | 59.75 ± 7.94 | 68.44 ± 24.62 | 0.67 |
Monocytes | 3.45 ± 0.50 | 0.96 ± 0.27 | <0.0001 b | 0.88 ± 0.29 | 0.55 ± 0.16 | 0.77 |
Monocytes (after removing non-hematopoietic cells) | 5.35 ± 0.78 | 4.56 ± 1.27 | 0.07 | 4.33 ± 1.44 | 3.17 ± 0.93 | 0.93 |
Classical | 82.08 ± 1.63 | 81.87 ± 2.68 | 0.43 | 80.37 ± 3.97 | 84.07 ± 3.19 | 0.96 |
CD206+ | 43.04 ± 5.33 | 43.04 ± 6.46 | 0.93 | 49.70 ± 7.99 | 22.16 ± 9.36 | 0.02 * |
CD274+ | 57.03 ± 5.50 | 54.86 ± 6.26 | 0.82 | 62.40 ± 7.52 | 43.01 ± 10.49 | 0.03 * |
Intermediate | 11.38 ± 1.00 | 9.91 ± 1.40 | 0.17 | 10.85 ± 2.18 | 8.54 ± 1.33 | 0.98 |
CD206+ | 56.06 ± 5.08 | 48.95 ± 6.01 | 0.50 | 58.94 ± 7.19 | 28.29 ± 8.57 | 0.02 * |
CD274+ | 67.53 ± 4.80 | 59.93 ± 5.90 | 0.25 | 66.14 ± 7.47 | 41.96 ± 8.80 | 0.04 * |
Non-Classical | 6.01 ± 1.16 | 8.22 ± 2.66 | 0.17 | 8.81 ± 3.84 | 7.35 ± 3.50 | 0.38 |
CD206+ | 40.71 ± 5.00 | 31.97 ± 6.44 | 0.09 | 34.37 ± 7.91 | 22.86 ± 10.50 | 0.23 |
CD274+ | 56.04 ± 5.54 | 51.42 ± 6.32 | 0.46 | 54.60 ± 9.09 | 29.72 ± 10.73 | 0.03 * |
NK cells | 4.25 ± 0.46 | 0.37 ± 0.06 | <0.0001 b | 0.36 ± 0.08 | 0.29 ± 0.07 | >0.99 |
NK cells (after removing non-hematopoietic cells) | 6.60 ± 0.71 | 1.74 ± 0.29 | <0.0001 b | 1.75 ± 0.39 | 1.65 ± 0.38 | 0.44 |
Non-Hematopoietic cells | 35.49 ± 3.63 | 78.97 ± 2.37 | <0.0001 b | 79.64 ± 2.85 | 82.52 ± 4.19 | 0.72 |
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Sampaio-Ribeiro, G.; Ruivo, A.; Silva, A.; Santos, A.L.; Oliveira, R.C.; Gama, J.; Cipriano, M.A.; Tralhão, J.G.; Paiva, A. Innate Immune Cells in the Tumor Microenvironment of Liver Metastasis from Colorectal Cancer: Contribution to a Comprehensive Therapy. Cancers 2023, 15, 3222. https://doi.org/10.3390/cancers15123222
Sampaio-Ribeiro G, Ruivo A, Silva A, Santos AL, Oliveira RC, Gama J, Cipriano MA, Tralhão JG, Paiva A. Innate Immune Cells in the Tumor Microenvironment of Liver Metastasis from Colorectal Cancer: Contribution to a Comprehensive Therapy. Cancers. 2023; 15(12):3222. https://doi.org/10.3390/cancers15123222
Chicago/Turabian StyleSampaio-Ribeiro, Gabriela, Ana Ruivo, Ana Silva, Ana Lúcia Santos, Rui Caetano Oliveira, João Gama, Maria Augusta Cipriano, José Guilherme Tralhão, and Artur Paiva. 2023. "Innate Immune Cells in the Tumor Microenvironment of Liver Metastasis from Colorectal Cancer: Contribution to a Comprehensive Therapy" Cancers 15, no. 12: 3222. https://doi.org/10.3390/cancers15123222