nach oben

Erschienen in:

24.11.2021 | Original Article

Anti-PD1/PDL1 IgG subclass distribution in ten cancer types and anti-PD1 IgG4 as biomarker for the long time survival in NSCLC with anti-PD1 therapy

verfasst von: Qiaoyun Tan, Liyuan Dai, Yanrong Wang, Shuxia Liu, Te Liang, Rongrong Luo, Shasha Wang, Ning Lou, Haizhu Chen, Yu Zhou, Qiaofeng Zhong, Jianliang Yang, Puyuan Xing, Xingsheng Hu, Yutao Liu, Shengyu Zhou, Jiarui Yao, Di Wu, Zhishang Zhang, Le Tang, Xiaobo Yu, Xiaohong Han, Yuankai Shi

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 7/2022

Einloggen, um Zugang zu erhalten

Abstract

Background

Antibodies targeting programmed cell death-1(PD1) and its ligand (PDL1) have revolutionized cancer therapy. However, little is known about the preexisted anti-PD1/PDL1 autoantibodies (AAbs) distribution in multiple cancer types, nor is their potential biomarker role for anti-PD1 therapy.

Method

Plasma anti-PD1/PDL1 AAb IgG and subclasses (IgG1-4) were detected by enzyme-linked immune sorbent assay (ELISA) in 190 cancer patients, covering 10 cancer types (lung, breast, esophageal, colorectal, liver, prostatic, cervical, ovarian, gastric cancers and lymphoma), the comprehensive correlation of AAbs with multiple clinical parameters was analyzed. We further tested these AAbs in 76 non-small cell lung cancer (NSCLC) samples receiving anti-PD1 therapy, the association of AAbs level with survival was analyzed and validated in an independent cohort (n = 32).

Results

Anti-PD1/PDL1 AAb IgG were globally detected in 10 types of cancer patients. IgG1 and IgG2 were the major subtypes for anti-PD1/PDL1 AAbs. Correlation analysis revealed a distinct landscape between various cancer types. The random forest model indicated that IgG4 subtype was mostly associated with cancer. In discovery cohort of 76 NSCLC patients, high anti-PD1 IgG4 was associated with a reduced overall survival (OS, p = 0.019), not progression-free survival (PFS, p = 0.088). The negative association of anti-PD1 IgG4 with OS was validated in 32 NSCLC patients (p = 0.032).

Conclusion

This study reports for the first time the distribution of preexisted anti-PD1/PDL1 AAb IgG and subclasses across 10 cancer types. Moreover, the anti-PD1 AAb IgG4 subclass was identified to associate with OS, which may serve as a potential biomarker for anti-PD1 therapeutic survival benefit in NSCLC patients.

Nur mit Berechtigung zugänglich

Topalian SL, Drake CG, Pardoll DM (2015) Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer Cell 27:450–461CrossRef

Harel M, Ortenberg R, Varanasi SK, Mangalhara KC, Mardamshina M, Markovits E et al (2019) Proteomics of melanoma response to immunotherapy reveals mitochondrial dependence. Cell 179(1):236–250CrossRef

Wei SC, Duffy CR, Allison JP (2018) Fundamental Mechanisms of Immune Checkpoint Blockade Therapy. Cancer Discov 8:1069–1086CrossRef

Singh S, Hassan D, Aldawsari HM, Molugulu N, Shukla R, Kesharwani P (2020) Immune checkpoint inhibitors: a promising anticancer therapy. Drug Discov Today 25:223–229CrossRef

Hamid O, Robert C, Daud A, Hodi FS, Hwu WJ, Kefford R et al (2013) Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med 369:134–144CrossRef

Peters S, Kerr KM, Stahel R (2018) PD-1 blockade in advanced NSCLC: a focus on pembrolizumab. Cancer Treat Rev 62:39–49CrossRef

Motzer RJ, Rini BI, McDermott DF, Redman BG, Kuzel TM, Harrison MR et al (2015) Nivolumab for metastatic renal cell carcinoma: results of a randomized phase II trial. J Clin Oncol 33:1430–1437CrossRef

Lee HT, Lee SH, Heo YS (2019) Molecular interactions of antibody drugs targeting PD-1, PD-L1, and CTLA-4 in immuno-oncology. Molecules 24(6):1190CrossRef

Fridman WH, Pages F, Sautes-Fridman C, Galon J (2012) The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer 12:298–306CrossRef

10.

Zaenker P, Gray ES, Ziman MR (2016) Autoantibody production in cancer-the humoral immune response toward autologous antigens in cancer patients. Autoimmun Rev 15:477–483CrossRef

11.

Anderson KS, Sibani S, Wallstrom G, Qiu J, Mendoza EA, Raphael J et al (2011) Protein microarray signature of autoantibody biomarkers for the early detection of breast cancer. J Proteome Res 10:85–96CrossRef

12.

Song E, Oh HS, Jeon MJ, Chung KW, Hong SJ, Ryu JS et al (2019) The value of preoperative antithyroidperoxidase antibody as a novel predictor of recurrence in papillary thyroid carcinoma. Int J Cancer 144:1414–1420CrossRef

13.

Toi Y, Sugawara S, Sugisaka J, Ono H, Kawashima Y, Aiba T et al (2019) Profiling preexisting antibodies in patients treated with anti-PD-1 therapy for advanced non-small cell lung cancer. JAMA Oncol 5:376–383CrossRef

14.

Dong H, Strome SE, Matteson EL, Moder KG, Flies DB, Zhu G et al (2003) Costimulating aberrant T cell responses by B7–H1 autoantibodies in rheumatoid arthritis. J Clin Investig 111:363–370CrossRef

15.

Matsumoto K, Miyake Y, Matsushita H, Ohnishi A, Ikeda F, Shiraha H et al (2014) Anti-programmed cell death-1 antibody as a new serological marker for type 1 autoimmune hepatitis. J Gastroenterol Hepatol 29:110–115CrossRef

16.

Shi H, Ye J, Teng J, Yin Y, Hu Q, Wu X et al (2017) Elevated serum autoantibodies against co-inhibitory PD-1 facilitate T cell proliferation and correlate with disease activity in new-onset systemic lupus erythematosus patients. Arthritis Res Ther 19:52CrossRef

17.

Tan Q, Wang D, Yang J, Xing P, Yang S, Li Y et al (2020) Autoantibody profiling identifies predictive biomarkers of response to anti-PD1 therapy in cancer patients. Theranostics 10:6399–6410CrossRef

18.

Wilson DK, Rudolph FB, Quiocho FA (1991) Atomic structure of adenosine deaminase complexed with a transition-state analog: understanding catalysis and immunodeficiency mutations. Science 252:1278–1284CrossRef

19.

Dietterich TG (2000) An experimental comparison of three methods for constructing ensembles of decision trees: bagging, boosting, and randomization. Mach Learn 40:139–157CrossRef

20.

Li Y, Li CQ, Guo SJ, Guo W, Jiang HW, Li HC et al (2020) Longitudinal serum autoantibody repertoire profiling identifies surgery-associated biomarkers in lung adenocarcinoma. EBioMedicine 53:102674CrossRef

21.

Lam S, Boyle P, Healey GF, Maddison P, Peek L, Murray A et al (2011) EarlyCDT-Lung: an immunobiomarker test as an aid to early detection of lung cancer. Cancer Prev Res (Phila) 4:1126–1134CrossRef

22.

Hutter C, Zenklusen JC (2018) The cancer genome atlas: creating lasting value beyond its data. Cell 173:283–285CrossRef

23.

de Taeye SW, Rispens T, Vidarsson G (2019) The ligands for human IgG and their effector functions. Antibodies (Basel) 8(2):30CrossRef

24.

Engelmann R, Brandt J, Eggert M, Karberg K, Krause A, Neeck G et al (2008) IgG1 and IgG4 are the predominant subclasses among auto-antibodies against two citrullinated antigens in RA. Rheumatology (Oxford) 47:1489–1492CrossRef

25.

Akbay EA, Koyama S, Liu Y, Dries R, Bufe LE, Silkes M et al (2017) Interleukin-17A promotes lung tumor progression THROUGH neutrophil attraction to tumor sites and mediating resistance to PD-1 blockade. J Thorac Oncol 12:1268–1279CrossRef

26.

Liu Y, Liao XW, Qin YZ, Mo XW, Luo SS (2020) Identification of F5 as a prognostic biomarker in patients with gastric cancer. Biomed Res Int 2020:9280841PubMedPubMedCentral

27.

Wang L, Tsai TH, Huang CF, Ho MS, Lin DB, Ho YC et al (2007) Utilizing self-prepared ELISA plates for a cross-population study of different anti-HBe IgG subclass profiles. J Med Virol 79:495–502CrossRef

28.

Vidarsson G, Dekkers G, Rispens T (2014) IgG subclasses and allotypes: from structure to effector functions. Front Immunol 5:520CrossRef

29.

Yu J, Song Y, Tian W (2020) How to select IgG subclasses in developing anti-tumor therapeutic antibodies. J Hematol Oncol 13:45CrossRef

Titel: Anti-PD1/PDL1 IgG subclass distribution in ten cancer types and anti-PD1 IgG4 as biomarker for the long time survival in NSCLC with anti-PD1 therapy
verfasst von: Qiaoyun Tan
Liyuan Dai
Yanrong Wang
Shuxia Liu
Te Liang
Rongrong Luo
Shasha Wang
Ning Lou
Haizhu Chen
Yu Zhou
Qiaofeng Zhong
Jianliang Yang
Puyuan Xing
Xingsheng Hu
Yutao Liu
Shengyu Zhou
Jiarui Yao
Di Wu
Zhishang Zhang
Le Tang
Xiaobo Yu
Xiaohong Han
Yuankai Shi
Publikationsdatum: 24.11.2021
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 7/2022
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-021-03106-z

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Anti-PD1/PDL1 IgG subclass distribution in ten cancer types and anti-PD1 IgG4 as biomarker for the long time survival in NSCLC with anti-PD1 therapy