CD169+ Macrophages in Primary Breast Tumors Associate with Tertiary Lymphoid Structures, Tregs and a Worse Prognosis for Patients with Advanced Breast Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Ethical Declarations
2.2. Patient Cohorts and Study Design
2.3. Immunohistochemistry and Scoring
2.4. Statistical Analyses
2.5. Gene Expression Analyses
3. Results
3.1. CD169+ TAMs Associate with TLLSs in PTs
3.2. CD169+ TAMs and TLLSs as Prognostic Markers for Breast Cancer Patients
3.3. Treg Infiltration Impacts the Prognostic Effect of CD169+ TAMs
3.4. CD169+ TAMs and TLLSs Show Unique Independent Prognostic Effects
3.5. CD169+ TAMs Associate with Both Mature TLS and Breg Gene Signatures
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Patient Characteristics | No. of Patients | Percent (%) | |
---|---|---|---|
Age | >50 | 92 | 45.1 |
<50 | 112 | 54.9 | |
Tumor size (T) | T1 (0–20 mm) | 83 | 40.7 |
T2 (20–50 mm) | 95 | 46.6 | |
T3 (>50 mm) | 16 | 7.8 | |
T4 (Invasion) | 9 | 4.4 | |
Missing | 1 | 0.5 | |
Regional lymph nodes (N) | N0 | 65 | 31.9 |
N1 | 124 | 60.8 | |
N2 | 9 | 4.4 | |
N3 | 2 | 1.0 | |
Missing | 4 | 2.0 | |
Metastasis (M) | M0 | 185 | 90.7 |
M1 | 18 | 8.8 | |
Missing | 1 | 0.5 | |
PT receptor status | |||
ER | Neg | 36 | 17.6 |
Pos | 152 | 92.2 | |
Missing | 16 | 7.8 | |
PR | Neg | 80 | 39.2 |
Pos | 107 | 52.5 | |
Missing | 17 | 8.3 | |
HER2 | Neg | 172 | 84.3 |
Pos | 17 | 8.3 | |
Missing | 15 | 7.4 | |
LNM receptor status | |||
ER | Neg | 28 | 13.7 |
Pos | 74 | 36.3 | |
Missing | 102 | 50.0 | |
PR | Neg | 64 | 31.4 |
Pos | 38 | 18.6 | |
Missing | 102 | 50.0 | |
HER2 | Neg | 77 | 37.7 |
Pos | 13 | 6.4 | |
Missing | 114 | 55.9 | |
Adjuvant therapy given | |||
Chemotherapy | No | 106 | 52.0 |
Yes | 98 | 48.0 | |
Endocrine | No | 92 | 45.1 |
Yes | 112 | 54.9 | |
Radiotherapy | No | 55 | 27.0 |
Yes | 149 | 73.0 |
Clinicopathological Features | CD169+ PT | CD169+ LNM | |||||||
---|---|---|---|---|---|---|---|---|---|
OR | 95% CI | p-Value a | n | OR | 95% CI | p-Value a | n | ||
Age | >50 | 85 | 1 | 48 | |||||
<50 | 0.96 | 0.51–1.81 | 0.90 | 106 | 0.89 | 0.43–1.88 | 0.77 | 67 | |
Overall Survival | >5 years | 1 | 67 | 1 | 42 | ||||
<5 years | 1.21 | 0.61–2.36 | 0.59 | 124 | 2.20 | 1.01–4.79 | 0.045 | 73 | |
Relapse free interval | >5 years | 1 | 108 | 1 | 77 | ||||
<5 years | 0.61 | 0.31–1.22 | 0.16 | 73 | 1.37 | 0.61–3.06 | 0.44 | 35 | |
Tumor size | T1 | 1 | 80 | 1 | 34 | ||||
>T1 | 0.47 | 0.24–0.89 | 0.019 | 110 | 0.42 | 0.19–0.97 | 0.041 | 80 | |
Ki67+ PT | Neg | 1 | 24 | 1 | 37 | ||||
Pos | 2.33 | 1.183–4.600 | 0.021 | 24 | 1.26 | 0.535–2.989 | 0.67 b | 16 | |
Ki67+ LNM | Neg | 1 | 14 | 1 | 31 | ||||
Pos | 1.47 | 0.550–3.923 | 0.45b | 9 | 0.69 | 0.285–1.662 | 0.51b | 12 | |
ER PT | Neg | 1 | 36 | 1 | 21 | ||||
Pos | 0.28 | 0.13–0.60 | 0.001 | 147 | 1.43 | 0.55–3.75 | 0.63 | 85 | |
ER LNM | Neg | 1 | 24 | 1 | 28 | ||||
Pos | 0.76 | 0.26–2.28 | 0.77 | 69 | 0.53 | 0.22–1.29 | 0.18 | 70 | |
PR PT | Neg | 1 | 79 | 1 | 42 | ||||
Pos | 0.59 | 0.31–1.12 | 0.11 | 103 | 1.18 | 0.54–2.59 | 0.68 | 61 | |
PR LNM | Neg | 1 | 57 | 1 | 60 | ||||
Pos | 0.34 | 0.11–1.01 | 0.053 | 37 | 0.68 | 0.30–1.56 | 0.36 | 37 | |
HER2 PT | Neg | 1 | 166 | 1 | 95 | ||||
Pos | 1.77 | 0.61–5.17 | 0.37b | 16 | 0.65 | 0.17–2.46 | 0.74 b | 10 | |
HER2 LNM | Neg | 1 | 69 | 1 | 77 | ||||
Pos | 0.99 | 0.24–4.06 | 1b | 13 | 1.41 | 0.41–4.76 | 0.76 b | 12 | |
Cell infiltration association | |||||||||
FoxP3 PT | Neg | 1 | 68 | 1 | 40 | ||||
Pos | 2.06 | 0.99–4.26 | 0.057 | 107 | 0.76 | 0.34–1.72 | 0.51 | 56 | |
FoxP3 LNM | Neg | 1 | 24 | 1 | 26 | ||||
Pos | 0.70 | 0.23–2.13 | 0.57 | 49 | 2.87 | 0.99–8.27 | 0.046 | 54 | |
TLLS PT | Neg | 1 | 165 | 1 | 91 | ||||
Pos | 3.77 | 1.61–8.82 | 0.004 | 26 | 2.04 | 0.58–7.27 | 0.36 b | 12 | |
TLLS LNM | Neg | 1 | 39 | 1 | 46 | ||||
Pos | 1.02 | 0.40–2.62 | 0.97 | 64 | 4.76 | 2.12–10.71 | 0.0001 | 69 |
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Share and Cite
Briem, O.; Källberg, E.; Kimbung, S.; Veerla, S.; Stenström, J.; Hatschek, T.; Hagerling, C.; Hedenfalk, I.; Leandersson, K. CD169+ Macrophages in Primary Breast Tumors Associate with Tertiary Lymphoid Structures, Tregs and a Worse Prognosis for Patients with Advanced Breast Cancer. Cancers 2023, 15, 1262. https://doi.org/10.3390/cancers15041262
Briem O, Källberg E, Kimbung S, Veerla S, Stenström J, Hatschek T, Hagerling C, Hedenfalk I, Leandersson K. CD169+ Macrophages in Primary Breast Tumors Associate with Tertiary Lymphoid Structures, Tregs and a Worse Prognosis for Patients with Advanced Breast Cancer. Cancers. 2023; 15(4):1262. https://doi.org/10.3390/cancers15041262
Chicago/Turabian StyleBriem, Oscar, Eva Källberg, Siker Kimbung, Srinivas Veerla, Jenny Stenström, Thomas Hatschek, Catharina Hagerling, Ingrid Hedenfalk, and Karin Leandersson. 2023. "CD169+ Macrophages in Primary Breast Tumors Associate with Tertiary Lymphoid Structures, Tregs and a Worse Prognosis for Patients with Advanced Breast Cancer" Cancers 15, no. 4: 1262. https://doi.org/10.3390/cancers15041262