Activated Eosinophils Predict Longer Progression-Free Survival under Immune Checkpoint Inhibition in Melanoma
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patient Collective and Clinical Data
2.2. Immunofluorescence Co-Staining of Eosinophils and Effector T-Cells in Tissue Microarrays
2.3. Microscopic Analysis of Fluorescent Stained Tissue Samples
2.4. Determination of ECP and EPX Serum Levels
2.5. Statistical Analysis
3. Results
3.1. TMA Expression Analysis—Patient Characteristics
3.2. Quantification of Tumor-Infiltrating Eosinophils
3.3. Quantification of Tumor-Infiltrating Effector T-Cells
3.4. Correlation of Tumor-Infiltrating Eosinophils and Effector T-Cells in Melanoma
3.5. Association between the Amount of Tumor-Infiltrated Activated Eosinophils as Well as Effector T-Cells and the Survival of Melanoma Patients
3.6. Blood-Based Analysis during ICI—Patient Characteristics
3.7. High Absolute Eosinophil Count and Elevated ECP Serum Levels Prior to ICI Initiation Are Related to Delayed Progression
3.8. Constant to Decreasing AEC and ECP Levels between Baseline and the Fourth Infusion Cycle of ICI Are Associated with Later Progression of Metastatic Melanoma
3.9. Responders and Non-Responders Do Not Differ in Peripheral Blood AEC, as Well as ECP and EPX Serum Levels
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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TMA Characteristics | n | % |
---|---|---|
Localisation of the nevus | 77 | 21.2 |
Trunk | 62 | 80.5 |
Extremities | 15 | 19.5 |
Localisation of the primary melanoma | 108 | 29.8 |
Trunk | 78 | 72.2 |
Extremities | 29 | 26.9 |
Unknown | 1 | 0.9 |
Localisation of the metastases | 177 | 48.9 |
Locoregional metastases | 157 | 88.7 |
Subcutaneous/Cutaneous | 75 | 47.8 |
Lymph nodes | 82 | 52.2 |
Distant metastases | 17 | 9.6 |
Unknown | 3 | 1.7 |
Histological subtype of the primary melanoma | 108 | 29.8 |
SSM | 25 | 23.1 |
NMM | 15 | 13.9 |
LMM | 6 | 5.6 |
ALM | 8 | 7.4 |
Other | 23 | 21.3 |
Unknown | 31 | 28.7 |
Breslow thickness of melanoma | 108 | 29.8 |
≤1 mm | 13 | 12.0 |
1–2 mm | 18 | 16.7 |
2–4 mm | 40 | 37.0 |
>4 mm | 10 | 9.3 |
Unknown | 27 | 25.0 |
Ulceration | 108 | 29.8 |
Yes | 34 | 31.5 |
No | 43 | 39.8 |
Unknown | 31 | 28.7 |
Correlation Between | Kendall’s Rank Correlation Coefficient (R) | p |
---|---|---|
Siglec-8 and CD8 | 0.42 | <0.0001 |
ECP and CD8 | 0.34 | <0.0001 |
EPX and CD8 | 0.41 | <0.0001 |
Patient Characteristics | n | % |
---|---|---|
Age (years) | ||
Median (range) | 60.9 (20–82) | |
Gender | ||
Male | 32 | 71.1 |
Female | 13 | 2.9 |
AJCC (eighth edition) | ||
III | 4 | 8.9 |
IV | 41 | 91.1 |
Lines of treatment | ||
First line | 29 | 64.4 |
Second line | 14 | 31.1 |
IFN therapy | 3 | 21.4 |
Chemotherapy | 2 | 14.3 |
BRAFi or BRAF/MEKi | 7 | 50 |
Pembrolizumab | 2 | 14.3 |
Third line | 2 | 44.4 |
Administered immune checkpoint inhibitors | ||
Ipilimumab + Nivolumab | 28 | 62.2 |
Nivolumab | 6 | 13.3 |
Pembrolizumab | 11 | 24.5 |
BRAFV600 mutation | ||
Yes | 19 | 42.2 |
No | 23 | 51.1 |
Unknown | 3 | 6.7 |
Immune-related adverse events | ||
Grade I or II | 16 | 35.6 |
Grade III or IV | 10 | 22.2 |
Clinical response (according to RECIST 1.1) | ||
CR | 13 | 28.9 |
PR | 16 | 35.6 |
SD | 5 | 11.1 |
PD | 11 | 24.4 |
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Ammann, N.L.; Schwietzer, Y.F.; Mess, C.; Stadler, J.-C.; Geidel, G.; Kött, J.; Pantel, K.; Schneider, S.W.; Utikal, J.; Bauer, A.T.; et al. Activated Eosinophils Predict Longer Progression-Free Survival under Immune Checkpoint Inhibition in Melanoma. Cancers 2022, 14, 5676. https://doi.org/10.3390/cancers14225676
Ammann NL, Schwietzer YF, Mess C, Stadler J-C, Geidel G, Kött J, Pantel K, Schneider SW, Utikal J, Bauer AT, et al. Activated Eosinophils Predict Longer Progression-Free Survival under Immune Checkpoint Inhibition in Melanoma. Cancers. 2022; 14(22):5676. https://doi.org/10.3390/cancers14225676
Chicago/Turabian StyleAmmann, Nadine L., Yasmin F. Schwietzer, Christian Mess, Julia-Christina Stadler, Glenn Geidel, Julian Kött, Klaus Pantel, Stefan W. Schneider, Jochen Utikal, Alexander T. Bauer, and et al. 2022. "Activated Eosinophils Predict Longer Progression-Free Survival under Immune Checkpoint Inhibition in Melanoma" Cancers 14, no. 22: 5676. https://doi.org/10.3390/cancers14225676