Deep learning-based scoring of tumour-infiltrating lymphocytes is prognostic in primary melanoma and predictive to PD-1 checkpoint inhibition in melanoma metastases
Background - Recent advances in digital pathology have enabled accurate and standardised enumeration of tumour-infiltrating lymphocytes (TILs). Here, we aim to evaluate TILs as a percentage electronic TIL score (eTILs) and investigate its prognostic and predictive relevance in cutaneous melanoma. -...
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| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
July 2023
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| In: |
EBioMedicine
Year: 2023, Volume: 93, Pages: 1-19 |
| ISSN: | 2352-3964 |
| DOI: | 10.1016/j.ebiom.2023.104644 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.ebiom.2023.104644 Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S2352396423002098 
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| Author Notes: | Eftychia Chatziioannou, Jana Roßner, Thazin New Aung, David L. Rimm, Heike Niessner, Ulrike Keim, Lina Maria Serna-Higuita, Irina Bonzheim, Luis Kuhn Cuellar, Dana Westphal, Julian Steininger, Friedegund Meier, Oltin Tiberiu Pop, Stephan Forchhammer, Lukas Flatz, Thomas Eigentler, Claus Garbe, Martin Röcken, Teresa Amaral and Tobias Sinnberg |
| Summary: | Background - Recent advances in digital pathology have enabled accurate and standardised enumeration of tumour-infiltrating lymphocytes (TILs). Here, we aim to evaluate TILs as a percentage electronic TIL score (eTILs) and investigate its prognostic and predictive relevance in cutaneous melanoma. - Methods - We included stage I to IV cutaneous melanoma patients and used hematoxylin-eosin-stained slides for TIL analysis. We assessed eTILs as a continuous and categorical variable using the published cut-off of 16.6% and applied Cox regression models to evaluate associations of eTILs with relapse-free, distant metastasis-free, and overall survival. We compared eTILs of the primaries with matched metastasis. Moreover, we assessed the predictive relevance of eTILs in therapy-naïve metastases according to the first-line therapy. - Findings - We analysed 321 primary cutaneous melanomas and 191 metastatic samples. In simple Cox regression, tumour thickness (p < 0.0001), presence of ulceration (p = 0.0001) and eTILs ≤16.6% (p = 0.0012) were found to be significant unfavourable prognostic factors for RFS. In multiple Cox regression, eTILs ≤16.6% (p = 0.0161) remained significant and downgraded the current staging. Lower eTILs in the primary tissue was associated with unfavourable relapse-free (p = 0.0014) and distant metastasis-free survival (p = 0.0056). In multiple Cox regression adjusted for tumour thickness and ulceration, eTILs as continuous remained significant (p = 0.019). When comparing TILs in primary tissue and corresponding metastasis of the same patient, eTILs in metastases was lower than in primary melanomas (p < 0.0001). In therapy-naïve metastases, an eTILs >12.2% was associated with longer progression-free survival (p = 0.037) and melanoma-specific survival (p = 0.0038) in patients treated with anti-PD-1-based immunotherapy. In multiple Cox regression, lactate dehydrogenase (p < 0.0001) and eTILs ≤12.2% (p = 0.0130) were significantly associated with unfavourable melanoma-specific survival. - Interpretation - Assessment of TILs is prognostic in primary melanoma samples, and the eTILs complements staging. In therapy-naïve metastases, eTILs ≤12.2% is predictive of unfavourable survival outcomes in patients receiving anti-PD-1-based therapy. - Funding - See a detailed list of funding bodies in the Acknowledgements section at the end of the manuscript. |
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| Item Description: | Online veröffentlicht: 7. Juni 2023 Gesehen am 29.08.2023 |
| Physical Description: | Online Resource |
| ISSN: | 2352-3964 |
| DOI: | 10.1016/j.ebiom.2023.104644 |