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. -...
Gespeichert in:
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
July 2023
|
| In: |
EBioMedicine
Year: 2023, Jahrgang: 93, Pages: 1-19 |
| ISSN: | 2352-3964 |
| DOI: | 10.1016/j.ebiom.2023.104644 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.ebiom.2023.104644 Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S2352396423002098 
|
| Verfasserangaben: | 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 |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1858165601 | ||
| 003 | DE-627 | ||
| 005 | 20240329080553.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 230829s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.ebiom.2023.104644 |2 doi | |
| 035 | |a (DE-627)1858165601 | ||
| 035 | |a (DE-599)KXP1858165601 | ||
| 035 | |a (OCoLC)1425212510 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Chatziioannou, Eftychia |e VerfasserIn |0 (DE-588)130037876X |0 (DE-627)1858166470 |4 aut | |
| 245 | 1 | 0 | |a Deep learning-based scoring of tumour-infiltrating lymphocytes is prognostic in primary melanoma and predictive to PD-1 checkpoint inhibition in melanoma metastases |c 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 |
| 264 | 1 | |c July 2023 | |
| 300 | |a 19 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Online veröffentlicht: 7. Juni 2023 | ||
| 500 | |a Gesehen am 29.08.2023 | ||
| 520 | |a 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. | ||
| 650 | 4 | |a Cutaneous melanoma | |
| 650 | 4 | |a Digital pathology | |
| 650 | 4 | |a Predictive biomarkers | |
| 650 | 4 | |a Prognostic biomarkers | |
| 650 | 4 | |a Tumour-infiltrating lymphocytes | |
| 700 | 1 | |a Roßner, Jana |e VerfasserIn |0 (DE-588)1300379111 |0 (DE-627)1858167159 |4 aut | |
| 700 | 1 | |a Aung, Thazin New |e VerfasserIn |4 aut | |
| 700 | 1 | |a Rimm, David L. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Niessner, Heike |e VerfasserIn |4 aut | |
| 700 | 1 | |a Keim, Ulrike |e VerfasserIn |4 aut | |
| 700 | 1 | |a Serna-Higuita, Lina Maria |e VerfasserIn |4 aut | |
| 700 | 1 | |a Bonzheim, Irina |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kuhn Cuellar, Luis |e VerfasserIn |4 aut | |
| 700 | 1 | |a Westphal, Dana |e VerfasserIn |4 aut | |
| 700 | 1 | |a Steininger, Julian |e VerfasserIn |4 aut | |
| 700 | 1 | |a Meier, Friedegund |e VerfasserIn |4 aut | |
| 700 | 1 | |a Pop, Oltin Tiberiu |e VerfasserIn |4 aut | |
| 700 | 1 | |a Forchhammer, Stephan |e VerfasserIn |4 aut | |
| 700 | 1 | |a Flatz, Lukas |e VerfasserIn |4 aut | |
| 700 | 1 | |a Eigentler, Thomas |e VerfasserIn |4 aut | |
| 700 | 1 | |a Garbe, Claus |d 1951- |e VerfasserIn |0 (DE-588)108397041 |0 (DE-627)516177893 |0 (DE-576)171143817 |4 aut | |
| 700 | 1 | |a Röcken, Martin |d 1956- |e VerfasserIn |0 (DE-588)111305314 |0 (DE-627)688133959 |0 (DE-576)167012436 |4 aut | |
| 700 | 1 | |a Amaral, Teresa |e VerfasserIn |0 (DE-588)1219099643 |0 (DE-627)1734832150 |4 aut | |
| 700 | 1 | |a Sinnberg, Tobias |e VerfasserIn |0 (DE-588)1022422243 |0 (DE-627)71696807X |0 (DE-576)365316008 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t EBioMedicine |d Amsterdam [u.a.] : Elsevier, 2014 |g 93(2023) vom: Juli, Artikel-ID 104644, Seite 1-19 |h Online-Ressource |w (DE-627)802540074 |w (DE-600)2799017-5 |w (DE-576)416965725 |x 2352-3964 |7 nnas |a Deep learning-based scoring of tumour-infiltrating lymphocytes is prognostic in primary melanoma and predictive to PD-1 checkpoint inhibition in melanoma metastases |
| 773 | 1 | 8 | |g volume:93 |g year:2023 |g month:07 |g elocationid:104644 |g pages:1-19 |g extent:19 |a Deep learning-based scoring of tumour-infiltrating lymphocytes is prognostic in primary melanoma and predictive to PD-1 checkpoint inhibition in melanoma metastases |
| 856 | 4 | 0 | |u https://doi.org/10.1016/j.ebiom.2023.104644 |x Verlag |x Resolving-System |z kostenfrei |3 Volltext |
| 856 | 4 | 0 | |u https://www.sciencedirect.com/science/article/pii/S2352396423002098 |x Verlag |z kostenfrei |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20230829 | ||
| 993 | |a Article | ||
| 994 | |a 2023 | ||
| 998 | |g 1300379111 |a Roßner, Jana |m 1300379111:Roßner, Jana |d 910000 |d 911300 |e 910000PR1300379111 |e 911300PR1300379111 |k 0/910000/ |k 1/910000/911300/ |p 2 | ||
| 999 | |a KXP-PPN1858165601 |e 4370787289 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"name":{"displayForm":["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"]},"relHost":[{"note":["Gesehen am 28.05.2020"],"pubHistory":["Volume 1 (2014)-"],"title":[{"title":"EBioMedicine","title_sort":"EBioMedicine"}],"type":{"media":"Online-Ressource","bibl":"periodical"},"origin":[{"dateIssuedKey":"2014","dateIssuedDisp":"2014-","publisherPlace":"Amsterdam [u.a.]","publisher":"Elsevier"}],"part":{"text":"93(2023) vom: Juli, Artikel-ID 104644, Seite 1-19","year":"2023","extent":"19","volume":"93","pages":"1-19"},"physDesc":[{"extent":"Online-Ressource"}],"disp":"Deep learning-based scoring of tumour-infiltrating lymphocytes is prognostic in primary melanoma and predictive to PD-1 checkpoint inhibition in melanoma metastasesEBioMedicine","language":["eng"],"id":{"issn":["2352-3964"],"zdb":["2799017-5"],"eki":["802540074"]},"recId":"802540074"}],"id":{"eki":["1858165601"],"doi":["10.1016/j.ebiom.2023.104644"]},"recId":"1858165601","language":["eng"],"physDesc":[{"extent":"19 S."}],"origin":[{"dateIssuedKey":"2023","dateIssuedDisp":"July 2023"}],"type":{"bibl":"article-journal","media":"Online-Ressource"},"title":[{"title_sort":"Deep learning-based scoring of tumour-infiltrating lymphocytes is prognostic in primary melanoma and predictive to PD-1 checkpoint inhibition in melanoma metastases","title":"Deep learning-based scoring of tumour-infiltrating lymphocytes is prognostic in primary melanoma and predictive to PD-1 checkpoint inhibition in melanoma metastases"}],"person":[{"given":"Eftychia","family":"Chatziioannou","display":"Chatziioannou, Eftychia","role":"aut"},{"role":"aut","display":"Roßner, Jana","given":"Jana","family":"Roßner"},{"role":"aut","family":"Aung","given":"Thazin New","display":"Aung, Thazin New"},{"role":"aut","display":"Rimm, David L.","family":"Rimm","given":"David L."},{"role":"aut","family":"Niessner","given":"Heike","display":"Niessner, Heike"},{"display":"Keim, Ulrike","given":"Ulrike","family":"Keim","role":"aut"},{"role":"aut","given":"Lina Maria","family":"Serna-Higuita","display":"Serna-Higuita, Lina Maria"},{"role":"aut","display":"Bonzheim, Irina","given":"Irina","family":"Bonzheim"},{"role":"aut","given":"Luis","family":"Kuhn Cuellar","display":"Kuhn Cuellar, Luis"},{"role":"aut","display":"Westphal, Dana","family":"Westphal","given":"Dana"},{"display":"Steininger, Julian","given":"Julian","family":"Steininger","role":"aut"},{"family":"Meier","given":"Friedegund","display":"Meier, Friedegund","role":"aut"},{"role":"aut","given":"Oltin Tiberiu","family":"Pop","display":"Pop, Oltin Tiberiu"},{"display":"Forchhammer, Stephan","given":"Stephan","family":"Forchhammer","role":"aut"},{"role":"aut","display":"Flatz, Lukas","family":"Flatz","given":"Lukas"},{"display":"Eigentler, Thomas","given":"Thomas","family":"Eigentler","role":"aut"},{"role":"aut","family":"Garbe","given":"Claus","display":"Garbe, Claus"},{"display":"Röcken, Martin","given":"Martin","family":"Röcken","role":"aut"},{"role":"aut","family":"Amaral","given":"Teresa","display":"Amaral, Teresa"},{"family":"Sinnberg","given":"Tobias","display":"Sinnberg, Tobias","role":"aut"}],"note":["Online veröffentlicht: 7. Juni 2023","Gesehen am 29.08.2023"]} | ||
| SRT | |a CHATZIIOANDEEPLEARNI2023 | ||