Association of Immune checkpoint inhibitor induced bullous pemphigoid with underlying cancer type: a lack of association with COL17A1 mutation and dysregulation: A lack of association with cancer tissue COL17A1 mutations and dysregulation

Rachel C. Chang; Henning Olbrich; Yulu F. Wang; Haley Gainer; Nina Curkovic; Theresa L. Walunas; Jessica Shiu; Parul Goyal; Adrian P. Mansini; Ralf J. Ludwig; Kyle T. Amber

doi:10.1016/j.xjidi.2026.100450

Association of Immune checkpoint inhibitor induced bullous pemphigoid with underlying cancer type: a lack of association with COL17A1 mutation and dysregulation: A lack of association with cancer tissue COL17A1 mutations and dysregulation

Rachel C. Chang, Henning Olbrich, Yulu F. Wang, Haley Gainer, Nina Curkovic, Theresa L. Walunas, Jessica Shiu, Parul Goyal, Adrian P. Mansini, Ralf J. Ludwig, Kyle T. Amber^*

^*Korrespondierende/r Autor/-in für diese Arbeit

Abstract

Bullous pemphigoid (BP) is an autoimmune blistering disease caused by autoantibodies to collagen type 17 (COL17A1) and is a recognized immune-related adverse event in patients receiving immune checkpoint inhibitors (ICIs). We investigated whether cancer type influences the risk of developing ICI-induced BP and whether COL17A1 mutations or dysregulation in tumor tissue contributes to disease-specific variation. Using TriNetX, systematic review, and bioinformatics datasets, we comprehensively assessed the associations of ICI-induced BP with different malignancy types as well as COL17A1 gene expression, mutation frequency, and immune correlations across cancers. Lung cancer was the most common underlying malignancy in ICI-induced BP, but nonmelanoma skin cancer and renal cell carcinoma had the highest relative risk, whereas lung cancer had the lowest. ICI-induced BP was associated with improved survival across several cancers. Urothelial cancer showed the shortest time to onset, whereas renal cell carcinoma showed the longest. Cutaneous squamous cell carcinoma and melanoma exhibited the highest COL17A1 mutation burden, whereas renal cell carcinoma had a low burden. COL17A1 was overexpressed in several cancers but underexpressed in melanoma, without strong correlation to tumor-infiltrating immune cells. Although the incidence of ICI-induced BP significantly differed on the basis of cancer type, COL17A1 mutations or dysregulation do not appear to drive this phenomenon, suggesting alternative immune mechanisms.

Originalsprache	Englisch
Aufsatznummer	100450
Zeitschrift	JID Innovations
Jahrgang	6
Ausgabenummer	2
Seiten (von - bis)	100450
DOIs	https://doi.org/10.1016/j.xjidi.2026.100450
Publikationsstatus	Veröffentlicht - 03.2026

Fördermittel

KTA is supported by the Swim Across America Foundation and the Buntrock Fund for Bullous Pemphigoid Research. HO and RJL are supported by the Cluster of Excellence Precision Medicine in Chronic Inflammation (EXC 2167), the collaborative research center 1526 (SFB 1526), and the Clinician Scientist School Lübeck (CS 012022) as well as the individual grant LU 877/25-1, all funded by the Deutsche Forschungsgemeinschaft and the Schleswig-Holstein Excellence-Chair Program from the State of Schleswig-Holstein. All authors consented to the publication of this manuscript, Conceptualization: KTA; Data Curation: RCC, HG, HO, NC, KTA; Formal Analysis: HO, YW, KTA; Investigation: RCC, HO, YW, HG, NC, KTA; Methodology: HO, APM, RL, KTA; Project Administration: KTA; Resources: RL, KTA; Supervision: RL, KTA; Visualization: RCC, HO, YW, KTA; Writing – Original Draft Preparation: RCC, HO, YW, HG, KTA; Writing – Review and Editing: RCC, HO, YW, HG, NC, TLW, JS, PG, APM, RL, KTA, The author(s) did not use AI/LLM in any part of the research process and/or manuscript preparation. KTA is supported by the Swim Across America Foundation and the Buntrock Fund for Bullous Pemphigoid Research. HO and RJL are supported by the Cluster of Excellence Precision Medicine in Chronic Inflammation (EXC 2167), the collaborative research center 1526 (SFB 1526), and the Clinician Scientist School Lübeck (CS 012022) as well as the individual grant LU 877/25-1, all funded by the Deutsche Forschungsgemeinschaft and the Schleswig-Holstein Excellence-Chair Program from the State of Schleswig-Holstein. All authors consented to the publication of this manuscript

Träger	Trägernummer
Swim Across America Foundation
Buntrock Fund for Bullous Pemphigoid Research	LU 877/25-1, SFB 1526, CS 012022

UN SDGs

Dieser Output leistet einen Beitrag zu folgendem(n) Ziel(en) für nachhaltige Entwicklung

SDG 3 – Gesundheit und Wohlergehen

Strategische Forschungsbereiche und Zentren

Forschungsschwerpunkt: Infektion und Entzündung - Zentrum für Infektions- und Entzündungsforschung Lübeck (ZIEL)
Zentren: Center for Research on Inflammation of the Skin (CRIS)

DFG-Fachsystematik

2.21-05 Immunologie
2.22-19 Dermatologie

Dokumente

10.1016/j.xjidi.2026.100450

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SFB 1526, PANTAU: Pathomechanismen Antikörpervermittelter Autoimmunerkrankungen
Sadik, C. (Sprecher*in), Zillikens, D. (Sprecher*in), Scheffold, A. (Projektleiter*in (PI)), Schmidt, E. (Projektleiter*in (PI)), Heine, G. (Projektleiter*in (PI)), Manz, R. (Projektleiter*in (PI)), Köhl, J. (Projektleiter*in (PI)), Ludwig, R. (Projektleiter*in (PI)), Peipp, M. (Projektleiter*in (PI)), Hammers, M. C. (Projektleiter*in (PI)), Verschoor, A. (Projektleiter*in (PI)), Karsten, C. (Projektleiter*in (PI)), Nimmerjahn, F. (Projektleiter*in (PI)), Hutloff, A. (Projektleiter*in (PI)), Ibrahim, S. (Projektleiter*in (PI)), Wettschureck, N. (Projektleiter*in (PI)), Bieber, K. (Projektleiter*in (PI)), Schilf, P. (Projektleiter*in (PI)), Vaeth, M. (Projektleiter*in (PI)), Hirose, M. (Projektleiter*in (PI)), Vaeth, M. (Projektleiter*in (PI)), Baines, J. F. (Projektleiter*in (PI)), Bacher, P. (Projektleiter*in (PI)), Hoffmann, M. (Projektleiter*in (PI)), Busch, H. S. (Projektleiter*in (PI)), Höppner, M. (Projektleiter*in (PI)), Becker, M. (Projektleiter*in (PI)), Holtsche, M. M. (Projektleiter*in (PI)), Fähnrich, A. (Projektleiter*in (PI)), Szymczak, S. (Projektleiter*in (PI)), Murthy, S. (Projektleiter*in (PI)) & Lux, A. (Projektleiter*in (PI))
01.01.22 → …
Projekt: DFG Verbundprojekte › DFG Sonderforschungsbereiche / Transregios (SFB/TR)

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Chang, R. C., Olbrich, H., Wang, Y. F., Gainer, H., Curkovic, N., Walunas, T. L., Shiu, J., Goyal, P., Mansini, A. P., Ludwig, R. J., & Amber, K. T. (2026). Association of Immune checkpoint inhibitor induced bullous pemphigoid with underlying cancer type: a lack of association with COL17A1 mutation and dysregulation: A lack of association with cancer tissue COL17A1 mutations and dysregulation. JID Innovations, 6(2), 100450. Artikel 100450. https://doi.org/10.1016/j.xjidi.2026.100450

@article{0f85d8f137864f5eb7de27c92b320b51,

title = "Association of Immune checkpoint inhibitor induced bullous pemphigoid with underlying cancer type: a lack of association with COL17A1 mutation and dysregulation: A lack of association with cancer tissue COL17A1 mutations and dysregulation",

abstract = "Bullous pemphigoid (BP) is an autoimmune blistering disease caused by autoantibodies to collagen type 17 (COL17A1) and is a recognized immune-related adverse event in patients receiving immune checkpoint inhibitors (ICIs). We investigated whether cancer type influences the risk of developing ICI-induced BP and whether COL17A1 mutations or dysregulation in tumor tissue contributes to disease-specific variation. Using TriNetX, systematic review, and bioinformatics datasets, we comprehensively assessed the associations of ICI-induced BP with different malignancy types as well as COL17A1 gene expression, mutation frequency, and immune correlations across cancers. Lung cancer was the most common underlying malignancy in ICI-induced BP, but nonmelanoma skin cancer and renal cell carcinoma had the highest relative risk, whereas lung cancer had the lowest. ICI-induced BP was associated with improved survival across several cancers. Urothelial cancer showed the shortest time to onset, whereas renal cell carcinoma showed the longest. Cutaneous squamous cell carcinoma and melanoma exhibited the highest COL17A1 mutation burden, whereas renal cell carcinoma had a low burden. COL17A1 was overexpressed in several cancers but underexpressed in melanoma, without strong correlation to tumor-infiltrating immune cells. Although the incidence of ICI-induced BP significantly differed on the basis of cancer type, COL17A1 mutations or dysregulation do not appear to drive this phenomenon, suggesting alternative immune mechanisms.",

author = "Chang, \{Rachel C.\} and Henning Olbrich and Wang, \{Yulu F.\} and Haley Gainer and Nina Curkovic and Walunas, \{Theresa L.\} and Jessica Shiu and Parul Goyal and Mansini, \{Adrian P.\} and Ludwig, \{Ralf J.\} and Amber, \{Kyle T.\}",

note = "Publisher Copyright: {\textcopyright} 2026 The Author(s)",

year = "2026",

month = mar,

doi = "10.1016/j.xjidi.2026.100450",

language = "English",

volume = "6",

pages = "100450",

journal = "JID Innovations",

issn = "2667-0267",

publisher = "Elsevier Inc.",

number = "2",

}

Chang, RC, Olbrich, H, Wang, YF, Gainer, H, Curkovic, N, Walunas, TL, Shiu, J, Goyal, P, Mansini, AP, Ludwig, RJ & Amber, KT 2026, 'Association of Immune checkpoint inhibitor induced bullous pemphigoid with underlying cancer type: a lack of association with COL17A1 mutation and dysregulation: A lack of association with cancer tissue COL17A1 mutations and dysregulation', JID Innovations, Jg. 6, Nr. 2, 100450, S. 100450. https://doi.org/10.1016/j.xjidi.2026.100450

Association of Immune checkpoint inhibitor induced bullous pemphigoid with underlying cancer type: a lack of association with COL17A1 mutation and dysregulation: A lack of association with cancer tissue COL17A1 mutations and dysregulation. / Chang, Rachel C.; Olbrich, Henning; Wang, Yulu F. et al.
in: JID Innovations, Jahrgang 6, Nr. 2, 100450, 03.2026, S. 100450.

Publikation: Beiträge in Fachzeitschriften › Zeitschriftenaufsätze › Forschung › Begutachtung

TY - JOUR

T1 - Association of Immune checkpoint inhibitor induced bullous pemphigoid with underlying cancer type: a lack of association with COL17A1 mutation and dysregulation

T2 - A lack of association with cancer tissue COL17A1 mutations and dysregulation

AU - Chang, Rachel C.

AU - Olbrich, Henning

AU - Wang, Yulu F.

AU - Gainer, Haley

AU - Curkovic, Nina

AU - Walunas, Theresa L.

AU - Shiu, Jessica

AU - Goyal, Parul

AU - Mansini, Adrian P.

AU - Ludwig, Ralf J.

AU - Amber, Kyle T.

PY - 2026/3

Y1 - 2026/3

N2 - Bullous pemphigoid (BP) is an autoimmune blistering disease caused by autoantibodies to collagen type 17 (COL17A1) and is a recognized immune-related adverse event in patients receiving immune checkpoint inhibitors (ICIs). We investigated whether cancer type influences the risk of developing ICI-induced BP and whether COL17A1 mutations or dysregulation in tumor tissue contributes to disease-specific variation. Using TriNetX, systematic review, and bioinformatics datasets, we comprehensively assessed the associations of ICI-induced BP with different malignancy types as well as COL17A1 gene expression, mutation frequency, and immune correlations across cancers. Lung cancer was the most common underlying malignancy in ICI-induced BP, but nonmelanoma skin cancer and renal cell carcinoma had the highest relative risk, whereas lung cancer had the lowest. ICI-induced BP was associated with improved survival across several cancers. Urothelial cancer showed the shortest time to onset, whereas renal cell carcinoma showed the longest. Cutaneous squamous cell carcinoma and melanoma exhibited the highest COL17A1 mutation burden, whereas renal cell carcinoma had a low burden. COL17A1 was overexpressed in several cancers but underexpressed in melanoma, without strong correlation to tumor-infiltrating immune cells. Although the incidence of ICI-induced BP significantly differed on the basis of cancer type, COL17A1 mutations or dysregulation do not appear to drive this phenomenon, suggesting alternative immune mechanisms.

AB - Bullous pemphigoid (BP) is an autoimmune blistering disease caused by autoantibodies to collagen type 17 (COL17A1) and is a recognized immune-related adverse event in patients receiving immune checkpoint inhibitors (ICIs). We investigated whether cancer type influences the risk of developing ICI-induced BP and whether COL17A1 mutations or dysregulation in tumor tissue contributes to disease-specific variation. Using TriNetX, systematic review, and bioinformatics datasets, we comprehensively assessed the associations of ICI-induced BP with different malignancy types as well as COL17A1 gene expression, mutation frequency, and immune correlations across cancers. Lung cancer was the most common underlying malignancy in ICI-induced BP, but nonmelanoma skin cancer and renal cell carcinoma had the highest relative risk, whereas lung cancer had the lowest. ICI-induced BP was associated with improved survival across several cancers. Urothelial cancer showed the shortest time to onset, whereas renal cell carcinoma showed the longest. Cutaneous squamous cell carcinoma and melanoma exhibited the highest COL17A1 mutation burden, whereas renal cell carcinoma had a low burden. COL17A1 was overexpressed in several cancers but underexpressed in melanoma, without strong correlation to tumor-infiltrating immune cells. Although the incidence of ICI-induced BP significantly differed on the basis of cancer type, COL17A1 mutations or dysregulation do not appear to drive this phenomenon, suggesting alternative immune mechanisms.

UR - https://www.scopus.com/pages/publications/105028568158

UR - https://www.mendeley.com/catalogue/708fbdcc-271c-34bc-add7-d9fb9758e658/

U2 - 10.1016/j.xjidi.2026.100450

DO - 10.1016/j.xjidi.2026.100450

M3 - Journal articles

AN - SCOPUS:105028568158

SN - 2667-0267

VL - 6

SP - 100450

JO - JID Innovations

JF - JID Innovations

IS - 2

M1 - 100450

ER -

Chang RC, Olbrich H, Wang YF, Gainer H, Curkovic N, Walunas TL et al. Association of Immune checkpoint inhibitor induced bullous pemphigoid with underlying cancer type: a lack of association with COL17A1 mutation and dysregulation: A lack of association with cancer tissue COL17A1 mutations and dysregulation. JID Innovations. 2026 Mär;6(2):100450. 100450. doi: 10.1016/j.xjidi.2026.100450

Association of Immune checkpoint inhibitor induced bullous pemphigoid with underlying cancer type: a lack of association with COL17A1 mutation and dysregulation: A lack of association with cancer tissue COL17A1 mutations and dysregulation

Abstract

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UN SDGs

Strategische Forschungsbereiche und Zentren

DFG-Fachsystematik

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Projekte

SFB 1526, PANTAU: Pathomechanismen Antikörpervermittelter Autoimmunerkrankungen

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