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^*

^*Corresponding author for this work

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.

Original language	English
Article number	100450
Journal	JID Innovations
Volume	6
Issue number	2
Pages (from-to)	100450
DOIs	https://doi.org/10.1016/j.xjidi.2026.100450
Publication status	Published - 03.2026

Funding

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research Areas and Centers

Academic Focus: Center for Infection and Inflammation Research (ZIEL)
Centers: Center for Research on Inflammation of the Skin (CRIS)

DFG Research Classification Scheme

2.21-05 Immunology
2.22-19 Dermatology

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10.1016/j.xjidi.2026.100450

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CRC 1526, PANTAU: Pathomechanisms of Antibody-mediated Autoimmunity
Sadik, C. (Speaker), Zillikens, D. (Speaker), Scheffold, A. (Principal Investigator (PI)), Schmidt, E. (Principal Investigator (PI)), Heine, G. (Principal Investigator (PI)), Manz, R. (Principal Investigator (PI)), Köhl, J. (Principal Investigator (PI)), Ludwig, R. (Principal Investigator (PI)), Peipp, M. (Principal Investigator (PI)), Hammers, M. C. (Principal Investigator (PI)), Verschoor, A. (Principal Investigator (PI)), Karsten, C. (Principal Investigator (PI)), Nimmerjahn, F. (Principal Investigator (PI)), Hutloff, A. (Principal Investigator (PI)), Ibrahim, S. (Principal Investigator (PI)), Wettschureck, N. (Principal Investigator (PI)), Bieber, K. (Principal Investigator (PI)), Schilf, P. (Principal Investigator (PI)), Vaeth, M. (Principal Investigator (PI)), Hirose, M. (Principal Investigator (PI)), Vaeth, M. (Principal Investigator (PI)), Baines, J. F. (Principal Investigator (PI)), Bacher, P. (Principal Investigator (PI)), Hoffmann, M. (Principal Investigator (PI)), Busch, H. S. (Principal Investigator (PI)), Höppner, M. (Principal Investigator (PI)), Becker, M. (Principal Investigator (PI)), Holtsche, M. M. (Principal Investigator (PI)), Fähnrich, A. (Principal Investigator (PI)), Szymczak, S. (Principal Investigator (PI)), Murthy, S. (Principal Investigator (PI)) & Lux, A. (Principal Investigator (PI))
01.01.22 → …
Project: DFG Joint Research › DFG Collaborative Research Centers (CRC)

Cite this

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. Article 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, vol. 6, no. 2, 100450, pp. 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, Vol. 6, No. 2, 100450, 03.2026, p. 100450.

Research output: Journal Articles › Journal articles › Research › peer-review

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 Mar;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

Funding

UN SDGs

Research Areas and Centers

DFG Research Classification Scheme

Access to Document

Other files and links

Fingerprint

Projects

CRC 1526, PANTAU: Pathomechanisms of Antibody-mediated Autoimmunity

Cite this