Clinical and molecular characteristics associated with response to therapeutic PD-1/PD-L1 inhibition in advanced Merkel cell carcinoma
Background Based on its viral-associated or UV-associated carcinogenesis, Merkel cell carcinoma (MCC) is a highly immunogenic skin cancer. Thus, clinically evident MCC occurs either in immuno-compromised patients or based on tumor-intrinsic immune escape mechanisms. This notion may explain that alth...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
24 January 2022
|
| In: |
Journal for ImmunoTherapy of Cancer
Year: 2022, Volume: 10, Issue: 1, Pages: 1-12 |
| ISSN: | 2051-1426 |
| DOI: | 10.1136/jitc-2021-003198 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1136/jitc-2021-003198 Verlag, lizenzpflichtig, Volltext: https://jitc.bmj.com/content/10/1/e003198 
|
| Author Notes: | Ivelina Spassova, Selma Ugurel, Linda Kubat, Lisa Zimmer, Patrick Terheyden, Annalena Mohr, Hannah Björn Andtback, Lisa Villabona, Ulrike Leiter, Thomas Eigentler, Carmen Loquai, Jessica C. Hassel, Thilo Gambichler, Sebastian Haferkamp, Peter Mohr, Claudia Pfoehler, Lucie Heinzerling, Ralf Gutzmer, Jochen S. Utikal, Kai Horny, Hans-Ulrich Schildhaus, Daniel Habermann, Daniel Hoffmann, Dirk Schadendorf, Jürgen Christian Becker |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1817687093 | ||
| 003 | DE-627 | ||
| 005 | 20251111095025.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 220928s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1136/jitc-2021-003198 |2 doi | |
| 035 | |a (DE-627)1817687093 | ||
| 035 | |a (DE-599)KXP1817687093 | ||
| 035 | |a (OCoLC)1361696039 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Spassova, Ivelina |e VerfasserIn |0 (DE-588)1225905044 |0 (DE-627)174594253X |4 aut | |
| 245 | 1 | 0 | |a Clinical and molecular characteristics associated with response to therapeutic PD-1/PD-L1 inhibition in advanced Merkel cell carcinoma |c Ivelina Spassova, Selma Ugurel, Linda Kubat, Lisa Zimmer, Patrick Terheyden, Annalena Mohr, Hannah Björn Andtback, Lisa Villabona, Ulrike Leiter, Thomas Eigentler, Carmen Loquai, Jessica C. Hassel, Thilo Gambichler, Sebastian Haferkamp, Peter Mohr, Claudia Pfoehler, Lucie Heinzerling, Ralf Gutzmer, Jochen S. Utikal, Kai Horny, Hans-Ulrich Schildhaus, Daniel Habermann, Daniel Hoffmann, Dirk Schadendorf, Jürgen Christian Becker |
| 264 | 1 | |c 24 January 2022 | |
| 300 | |a 12 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 28.09.2022 | ||
| 520 | |a Background Based on its viral-associated or UV-associated carcinogenesis, Merkel cell carcinoma (MCC) is a highly immunogenic skin cancer. Thus, clinically evident MCC occurs either in immuno-compromised patients or based on tumor-intrinsic immune escape mechanisms. This notion may explain that although advanced MCC can be effectively restrained by treatment with PD-1/PD-L1 immune checkpoint inhibitors (ICIs), a considerable percentage of patients does not benefit from ICI therapy. Biomarkers predicting ICI treatment response are currently not available. - Methods The present multicenter retrospective study investigated clinical and molecular characteristics in 114 patients with unresectable MCC at baseline before treatment with ICI for their association with therapy response (best overall response, BOR). In a subset of 21 patients, pretreatment tumor tissue was analyzed for activation, differentiation and spatial distribution of tumor infiltrating lymphocytes (TIL). - Results Of the 114 patients, n=74 (65%) achieved disease control (BOR=complete response/partial response/stable disease) on ICI. A Bayesian cumulative ordinal regression model revealed absence of immunosuppression and a limited number of tumor-involved organ systems was highly associated with a favorable therapy response. Unimpaired overall performance status, high age, normal serum lactate dehydrogenase and normal serum C reactive protein were moderately associated with disease control. While neither tumor Merkel cell polyomavirus nor tumor PD-L1 status showed a correlation with therapy response, treatment with anti-PD-1 antibodies was associated with a higher probability of disease control than treatment with anti-PD-L1 antibodies. Multiplexed immunohistochemistry demonstrated the predominance of CD8+ effector and central memory T cells (TCM) in close proximity to tumor cells in patients with a favorable therapy response. - Conclusions Our findings indicate the absence of immunosuppression, a limited number of tumor-affected organs, and a predominance of CD8+ TCM among TIL, as baseline parameters associated with a favorable response to PD-1/PD-L1 ICI therapy of advanced MCC. These factors should be considered when making treatment decisions in MCC patients. | ||
| 650 | 4 | |a costimulatory and inhibitory T-cell receptors | |
| 650 | 4 | |a immunotherapy | |
| 650 | 4 | |a lymphocytes | |
| 650 | 4 | |a skin neoplasms | |
| 650 | 4 | |a translational medical research | |
| 650 | 4 | |a tumor-Infiltrating | |
| 700 | 1 | |a Ugurel, Selma |d 1971- |e VerfasserIn |0 (DE-588)122030923 |0 (DE-627)081693532 |0 (DE-576)293057567 |4 aut | |
| 700 | 1 | |a Kubat, Linda |e VerfasserIn |4 aut | |
| 700 | 1 | |a Zimmer, Lisa |e VerfasserIn |4 aut | |
| 700 | 1 | |a Terheyden, Patrick |e VerfasserIn |4 aut | |
| 700 | 1 | |a Mohr, Annalena |e VerfasserIn |4 aut | |
| 700 | 1 | |a Andtback, Hannah Björn |e VerfasserIn |4 aut | |
| 700 | 1 | |a Villabona, Lisa |e VerfasserIn |4 aut | |
| 700 | 1 | |a Leiter, Ulrike |e VerfasserIn |4 aut | |
| 700 | 1 | |a Eigentler, Thomas |e VerfasserIn |4 aut | |
| 700 | 1 | |a Loquai, Carmen |e VerfasserIn |4 aut | |
| 700 | 1 | |a Hassel, Jessica C. |d 1975- |e VerfasserIn |0 (DE-588)129790702 |0 (DE-627)480399069 |0 (DE-576)29783715X |4 aut | |
| 700 | 1 | |a Gambichler, Thilo |e VerfasserIn |4 aut | |
| 700 | 1 | |a Haferkamp, Sebastian |e VerfasserIn |4 aut | |
| 700 | 1 | |a Mohr, Peter |e VerfasserIn |4 aut | |
| 700 | 1 | |a Pfoehler, Claudia |e VerfasserIn |4 aut | |
| 700 | 1 | |a Heinzerling, Lucie |e VerfasserIn |4 aut | |
| 700 | 1 | |a Gutzmer, Ralf |e VerfasserIn |4 aut | |
| 700 | 1 | |a Utikal, Jochen |d 1974- |e VerfasserIn |0 (DE-588)1026463750 |0 (DE-627)726765015 |0 (DE-576)371816580 |4 aut | |
| 700 | 1 | |a Horny, Kai |e VerfasserIn |4 aut | |
| 700 | 1 | |a Schildhaus, Hans-Ulrich |e VerfasserIn |4 aut | |
| 700 | 1 | |a Habermann, Daniel |e VerfasserIn |4 aut | |
| 700 | 1 | |a Hoffmann, Daniel |e VerfasserIn |4 aut | |
| 700 | 1 | |a Schadendorf, Dirk |d 1960- |e VerfasserIn |0 (DE-588)11142576X |0 (DE-627)499566076 |0 (DE-576)289702275 |4 aut | |
| 700 | 1 | |a Becker, Jürgen Christian |e VerfasserIn |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal for ImmunoTherapy of Cancer |d London : BioMed Central, 2013 |g 10(2022), 1, Artikel-ID e003198, Seite 1-12 |h Online-Ressource |w (DE-627)750086335 |w (DE-600)2719863-7 |w (DE-576)383767369 |x 2051-1426 |7 nnas |a Clinical and molecular characteristics associated with response to therapeutic PD-1/PD-L1 inhibition in advanced Merkel cell carcinoma |
| 773 | 1 | 8 | |g volume:10 |g year:2022 |g number:1 |g elocationid:e003198 |g pages:1-12 |g extent:12 |a Clinical and molecular characteristics associated with response to therapeutic PD-1/PD-L1 inhibition in advanced Merkel cell carcinoma |
| 856 | 4 | 0 | |u https://doi.org/10.1136/jitc-2021-003198 |x Verlag |x Resolving-System |z lizenzpflichtig |3 Volltext |
| 856 | 4 | 0 | |u https://jitc.bmj.com/content/10/1/e003198 |x Verlag |z lizenzpflichtig |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20220928 | ||
| 993 | |a Article | ||
| 994 | |a 2022 | ||
| 998 | |g 11142576X |a Schadendorf, Dirk |m 11142576X:Schadendorf, Dirk |d 50000 |e 50000PS11142576X |k 0/50000/ |p 24 | ||
| 998 | |g 1026463750 |a Utikal, Jochen |m 1026463750:Utikal, Jochen |d 60000 |e 60000PU1026463750 |k 0/60000/ |p 19 | ||
| 998 | |g 129790702 |a Hassel, Jessica C. |m 129790702:Hassel, Jessica C. |d 910000 |d 911300 |d 50000 |e 910000PH129790702 |e 911300PH129790702 |e 50000PH129790702 |k 0/910000/ |k 1/910000/911300/ |k 0/50000/ |p 12 | ||
| 998 | |g 122030923 |a Ugurel, Selma |m 122030923:Ugurel, Selma |d 60000 |e 60000PU122030923 |k 0/60000/ |p 2 | ||
| 999 | |a KXP-PPN1817687093 |e 4192870347 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"name":{"displayForm":["Ivelina Spassova, Selma Ugurel, Linda Kubat, Lisa Zimmer, Patrick Terheyden, Annalena Mohr, Hannah Björn Andtback, Lisa Villabona, Ulrike Leiter, Thomas Eigentler, Carmen Loquai, Jessica C. Hassel, Thilo Gambichler, Sebastian Haferkamp, Peter Mohr, Claudia Pfoehler, Lucie Heinzerling, Ralf Gutzmer, Jochen S. Utikal, Kai Horny, Hans-Ulrich Schildhaus, Daniel Habermann, Daniel Hoffmann, Dirk Schadendorf, Jürgen Christian Becker"]},"person":[{"given":"Ivelina","role":"aut","display":"Spassova, Ivelina","family":"Spassova"},{"family":"Ugurel","given":"Selma","role":"aut","display":"Ugurel, Selma"},{"family":"Kubat","role":"aut","given":"Linda","display":"Kubat, Linda"},{"family":"Zimmer","role":"aut","given":"Lisa","display":"Zimmer, Lisa"},{"family":"Terheyden","role":"aut","given":"Patrick","display":"Terheyden, Patrick"},{"given":"Annalena","role":"aut","display":"Mohr, Annalena","family":"Mohr"},{"family":"Andtback","role":"aut","given":"Hannah Björn","display":"Andtback, Hannah Björn"},{"display":"Villabona, Lisa","role":"aut","given":"Lisa","family":"Villabona"},{"family":"Leiter","display":"Leiter, Ulrike","role":"aut","given":"Ulrike"},{"family":"Eigentler","given":"Thomas","role":"aut","display":"Eigentler, Thomas"},{"family":"Loquai","role":"aut","given":"Carmen","display":"Loquai, Carmen"},{"family":"Hassel","display":"Hassel, Jessica C.","role":"aut","given":"Jessica C."},{"display":"Gambichler, Thilo","given":"Thilo","role":"aut","family":"Gambichler"},{"display":"Haferkamp, Sebastian","role":"aut","given":"Sebastian","family":"Haferkamp"},{"role":"aut","given":"Peter","display":"Mohr, Peter","family":"Mohr"},{"family":"Pfoehler","given":"Claudia","role":"aut","display":"Pfoehler, Claudia"},{"display":"Heinzerling, Lucie","given":"Lucie","role":"aut","family":"Heinzerling"},{"family":"Gutzmer","display":"Gutzmer, Ralf","given":"Ralf","role":"aut"},{"display":"Utikal, Jochen","role":"aut","given":"Jochen","family":"Utikal"},{"display":"Horny, Kai","given":"Kai","role":"aut","family":"Horny"},{"family":"Schildhaus","display":"Schildhaus, Hans-Ulrich","role":"aut","given":"Hans-Ulrich"},{"family":"Habermann","display":"Habermann, Daniel","role":"aut","given":"Daniel"},{"family":"Hoffmann","display":"Hoffmann, Daniel","role":"aut","given":"Daniel"},{"family":"Schadendorf","given":"Dirk","role":"aut","display":"Schadendorf, Dirk"},{"family":"Becker","role":"aut","given":"Jürgen Christian","display":"Becker, Jürgen Christian"}],"type":{"bibl":"article-journal","media":"Online-Ressource"},"origin":[{"dateIssuedKey":"2022","dateIssuedDisp":"24 January 2022"}],"recId":"1817687093","note":["Gesehen am 28.09.2022"],"relHost":[{"title":[{"title_sort":"Journal for ImmunoTherapy of Cancer","title":"Journal for ImmunoTherapy of Cancer","subtitle":"official journal of the Society for Immunotherapy of Cancer (SITC)"}],"language":["eng"],"part":{"issue":"1","pages":"1-12","extent":"12","year":"2022","text":"10(2022), 1, Artikel-ID e003198, Seite 1-12","volume":"10"},"pubHistory":["1.2013 -"],"physDesc":[{"extent":"Online-Ressource"}],"id":{"issn":["2051-1426"],"zdb":["2719863-7"],"eki":["750086335"]},"disp":"Clinical and molecular characteristics associated with response to therapeutic PD-1/PD-L1 inhibition in advanced Merkel cell carcinomaJournal for ImmunoTherapy of Cancer","note":["Gesehen am 29.06.20"],"recId":"750086335","origin":[{"publisherPlace":"London","dateIssuedKey":"2013","dateIssuedDisp":"2013-","publisher":"BioMed Central"}],"type":{"bibl":"periodical","media":"Online-Ressource"}}],"physDesc":[{"extent":"12 S."}],"id":{"eki":["1817687093"],"doi":["10.1136/jitc-2021-003198"]},"language":["eng"],"title":[{"title_sort":"Clinical and molecular characteristics associated with response to therapeutic PD-1/PD-L1 inhibition in advanced Merkel cell carcinoma","title":"Clinical and molecular characteristics associated with response to therapeutic PD-1/PD-L1 inhibition in advanced Merkel cell carcinoma"}]} | ||
| SRT | |a SPASSOVAIVCLINICALAN2420 | ||