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Antibody-mediated thyroid dysfunction during T-cell checkpoint blockade in patients with non-small-cell lung cancer
Open accessAbstract
Background Programmed cell death protein-1 (PD-1) blockade therapies have demonstrated durable responses and prolonged survival in a variety of malignancies. Treatment is generally well tolerated although immune-related adverse events (irAEs) can occur. Autoimmune thyroid dysfunction is among the most common irAE, but an assessment of the clinical, mechanistic, and immunologic features has not been previously described.Patient and methods Patients with advanced non-small-cell lung cancer (NSCLC) treated with pembrolizumab at Memorial Sloan Kettering Cancer Center (n = 51) as part of KEYNOTE-001 (NCT01295827) were included. Thyroid function test and anti-thyroid antibodies were assessed prospectively at each study visit, beginning before the first treatment. Frequency of development of thyroid dysfunction, association with anti-thyroid antibodies, clinical course, and relationship with progression-free survival and overall survival to treatment with pembrolizumab was evaluated.Results Of 51 patients treated, 3 were hypothyroid and 48 were not at baseline. Ten of 48 [21%, 95% confidence interval (CI) 10% to 35%] patients developed thyroid dysfunction requiring thyroid replacement. Anti-thyroid antibodies were present in 8 of 10 patients who developed thyroid dysfunction, compared with 3 of 38 who did not (80% versus 8%, P < 0.0001). Thyroid dysfunction occurred early (median, 42 days) in the pembrolizumab course, and a majority (6 of 10 patients) experienced brief, transient hyperthyroidism preceding the onset of hypothyroidism; no persistent hyperthyroidism occurred. Both hyperthyroidism and hypothyroidism were largely asymptomatic. Overall survival with pembrolizumab was significantly longer in subjects who developed thyroid dysfunction (hazard ratio, 0.29; 95% CI 0.09-0.94; P = 0.04).Conclusions Thyroid dysfunction during pembrolizumab treatment of NSCLC is common and is characterized by early-onset, frequently preceded by transient hyperthyroidism, closely associated with anti-thyroid antibodies, and may be associated with improved outcomes. The presence of antibody-mediated toxicity in T-cell-directed therapy suggests an under-recognized impact of PD-1 biology in modulating humoral immunity.
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“Two retrospective and two prospective studies reported that positive TPOAb and/or thyroglobulin autoantibodies (TgAb) are associated with a 40 to 70% risk of hypothyroidism during treatment”
From Graves’ Disease during Immune Checkpoint Inhibitor Therapy (A Case Series and Literature Review) (2021) · cites this paper as [56]
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“and that patients who had ICPi-induced hypothyroidism had positive anti-thyroid autoantibodies in 75 to 100% of cases [54,55,56,57].”
From Graves’ Disease during Immune Checkpoint Inhibitor Therapy (A Case Series and Literature Review) (2021) · cites this paper as [56]
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“Note that in the Osorio study [56], survival was better if patients developed ICPi-induced thyroid dysfunction”
From Graves’ Disease during Immune Checkpoint Inhibitor Therapy (A Case Series and Literature Review) (2021) · cites this paper as [56]
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PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
Hartkopf, A. D., Taran, F., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,989
Adverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review
Wanchoo, R., Karam, S., Uppal, N. N., Barta, V. S., Deray, G., Devoe, C., Launay‐Vacher, V., Jhaveri, K. D., & on behalf of Cancer and Kidney International Network Workgroup on Immune Checkpoint Inhibitors (2017) · American Journal of Nephrology · doi:10.1159/000455014 · Cited by 15,320
Pembrolizumab for the Treatment of Non–Small-Cell Lung Cancer
Garon, E. B., Rizvi, N. A., Hui, R., Leighl, N., Balmanoukian, A. S., Eder, J. P., Patnaik, A., Aggarwal, C., Gubens, M., Horn, L., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1501824 · Cited by 6,198
Self-citationHollowell, J. G., Staehling, N. W., Flanders, W. D., Hannon, W. H., Gunter, E. W., Spencer, C. A., & Braverman, L. E. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.87.2.489 · Cited by 4,279
Ishida, Y., Agata, Y., Shibahara, K., & Honjo, T. (1992) · The EMBO Journal · doi:10.1002/j.1460-2075.1992.tb05481.x · Cited by 3,259
Nishimura, H., Nose, M., Hiai, H., Minato, N., & Honjo, T. (1999) · Immunity · doi:10.1016/s1074-7613(00)80089-8 · Cited by 2,749
CTLA-4 and PD-1 Receptors Inhibit T-Cell Activation by Distinct Mechanisms
Parry, R. V., Chemnitz, J. M., Frauwirth, K. A., Lanfranco, A. R., Braunstein, I., Kobayashi, S. V., Linsley, P. S., Thompson, C. B., & Riley, J. L. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.21.9543-9553.2005 · Cited by 1,931
Garber, J. R., Cobin, R. H., Gharib, H., Hennessey, J. V., Klein, I., Mechanick, J. I., Pessah-Pollack, R., Singer, P. A., & Woeber, K. A. (2012) · Endocrine Practice · doi:10.4158/ep12280.gl · Cited by 1,567
Association of Pembrolizumab With Tumor Response and Survival Among Patients With Advanced Melanoma
Ribas, A., Hamid, O., Daud, A., Hodi, F. S., Wolchok, J. D., Kefford, R., Joshua, A. M., Patnaik, A., Hwu, W.-J., Weber, J. S., et al. (2016) · JAMA · doi:10.1001/jama.2016.4059 · Cited by 1,069
Self-citation2013 ETA Guideline: Management of Subclinical Hypothyroidism
Pearce, S. H. S., Brabant, G., Duntas, L. H., Monzani, F., Peeters, R. P., Razvi, S., & Wemeau, J.-L. (2013) · European Thyroid Journal · doi:10.1159/000356507 · Cited by 877
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Items 101–200 of 659
Pulmonary toxicity of immune checkpoint immunotherapy
Ghanbar, M., & Suresh, K. S. (2024) · Journal of Clinical Investigation · doi:10.1172/jci170503 · Cited by 80
“Similarly, thyroid dysfunction has also been linked to ICI therapy, with many patients who developed thyroiditis having evidence of circulating antithyroid antibodies either present at baseline or developed during treatment (93).”
BackgroundSafety and efficacy of PD-1/PD-L1 blockade in patients with preexisting antinuclear antibodies
Sakakida, T., Ishikawa, T., Chihara, Y., Harita, S., Uchino, J., Tabuchi, Y., Komori, S., Asai, J., Narukawa, T., Arai, A., et al. (2019) · Clinical & Translational Oncology · doi:10.1007/s12094-019-02214-8 · Cited by 73
“[19, 26] showed that preexisting antithyroid antibodies were highly correlated to subsequent thyroid dysfunction.”
BackgroundImmune-related adverse events of checkpoint inhibitors: Insights into immunological dysregulation
Yang, H., Yao, Z., Zhou, X., Zhang, W., Zhang, X., & Zhang, F. (2020) · Clinical Immunology · doi:10.1016/j.clim.2020.108377 · Cited by 77
How we treat endocrine complications of immune checkpoint inhibitors
Paschou, S. Α., Stefanaki, K., Ψαλτοπούλου, Θ., Liontos, M., Koutsoukos, K., Zagouri, F., Lambrinoudaki, I. V., & Dimopoulos, M. A. (2021) · ESMO Open · doi:10.1016/j.esmoop.2020.100011 · Cited by 74
Risk factors for immune-related adverse events: what have we learned and what lies ahead?
Liu, X., Shi, Y., Zhang, D., Zhou, Q., Liu, J., Chen, M., Xu, Y., Zhao, J., Zhong, W., & Wang, M. (2021) · Biomarker Research · doi:10.1186/s40364-021-00314-8 · Cited by 74
B Cells in Patients With Melanoma: Implications for Treatment With Checkpoint Inhibitor Antibodies
Willsmore, Z. N., Harris, R. J. C., Crescioli, S., Hussein, K., Kakkassery, H., Thapa, D., Cheung, A., Chauhan, J., Bax, H. J., Chenoweth, A. M., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2020.622442 · Cited by 72
“For example some patients suffering with CPI-induced hypothyroidism have raised titres of anti-thyroperoxidase antibody and/or anti-thyrotropin receptor antibodies (102,103).”
BackgroundDiagnosis and Management of Immune Related Adverse Events (irAEs) in Cancer Immunotherapy
Liu, Y., Zang, X.-Y., Wang, J., Huang, S., Jiang, X., & Zhang, P. (2019) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2019.109437 · Cited by 71
Cancer immunotherapy-induced endocrinopathies: Clinical behavior and therapeutic approach
Iglesias, P. (2017) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2017.08.019 · Cited by 70
Graves’ Disease Induced by Immune Checkpoint Inhibitors: A Case Report and Review of the Literature
Brancatella, A., Viola, N., Brogioni, S., Montanelli, L., Sardella, C., Vitti, P., Marcocci, C., Lupi, I., & Latrofa, F. (2019) · European Thyroid Journal · doi:10.1159/000501824 · Cited by 69
Ghosh, N., Postow, M. A., Zhu, C., Jannat‐Khah, D., Li, Q., Vitone, G., Chan, K. K., & Bass, A. R. (2022) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2021-004008 · Cited by 71
Remón, J., Mezquita, L., Corral, J., Vilariño, N., & Reguart, N. (2018) · Journal of Thoracic Disease · doi:10.21037/jtd.2017.12.52 · Cited by 68
“Hypothyroidism is frequently preceded by an earlier and transient period of asymptomatic hyperthyroidism induced by an acute inflammation of the thyroid gland (94).”
BackgroundInfluentialAdverse events associated with immune checkpoint inhibitor treatment for cancer
Esfahani, K., Meti, N., Miller, W. H., & Hudson, M. (2019) · Canadian Medical Association Journal · doi:10.1503/cmaj.180870 · Cited by 65
Autoantibodies in Patients With Immune-Related Adverse Events From Checkpoint Inhibitors
Ghosh, N., Chan, K. K., Jivanelli, B., & Bass, A. R. (2021) · JCR Journal of Clinical Rheumatology · doi:10.1097/rhu.0000000000001777 · Cited by 65
Seronegative antibody‐mediated neurology after immune checkpoint inhibitors
Wilson, R., Menassa, D. A., Davies, A. J., Michael, S., Hester, J., Küker, W., Collins, G. P., Cossins, J., Beeson, D., Steven, N. M., et al. (2018) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.547 · Cited by 69
“Indeed, the concept of an autoantibody-mediated condition is supported by the recent discovery of increased plasmablasts,(13) and a few organspecific autoantibodies, post-checkpoint inhibitors.(14) In addition to hypophysitis, neurological side effects of the checkpoint inhibitors include very few or single cases of a…”
BackgroundPercik, R., Shlomai, G., Tirosh, A., Tirosh, A., Leibowitz‐Amit, R., Eshet, Y., Greenberg, G., Merlinsky, A., Barhod, E., Steinberg‐Silman, Y., et al. (2019) · Autoimmunity Reviews · doi:10.1016/j.autrev.2019.102454 · Cited by 64
Thyroid dysfunction induced by nivolumab: searching for disease patterns and outcomes
Peiró, I., Palmero, R., Iglesias, P., Díez, J. J., Simó-Servat, A., Marín‐Jiménez, J. A., Jiménez, L., Domingo‐Doménech, E., Mancho-Fora, N., Nadal, E., et al. (2019) · Endocrine · doi:10.1007/s12020-019-01871-7 · Cited by 63
Keeping Expectations in Check With Immune Checkpoint Inhibitors
Temel, J. S., Gainor, J. F., Sullivan, R. J., & Greer, J. A. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2017.76.2146 · Cited by 62
Cortellini, A., Buti, S., Agostinelli, V., & Bersanelli, M. (2019) · Seminars in Oncology · doi:10.1053/j.seminoncol.2019.10.003 · Cited by 62
Wang, D., Chen, C., Gu, Y., Lu, W., Zhan, P., Liu, H., Lv, T., Song, Y., & Zhang, F. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.631949 · Cited by 62
Thyroid-related adverse events induced by immune checkpoint inhibitors
Chera, A., Stancu, A. L., & Bucur, O. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1010279 · Cited by 62
“Afterwards, thyroid autoantibodies should be measured (97) (pembrolizumab increases anti-thyroid peroxidase antibodies and anti-thyroglobulin antibodies in 80% of the patients with ICIinduced thyroid dysfunction) (158).”
BackgroundAso, M., Toi, Y., Sugisaka, J., Aiba, T., Kawana, S., Saito, R., Ogasawara, T., Tsurumi, K., Ono, K., Shimizu, H., et al. (2019) · The Oncologist · doi:10.1634/theoncologist.2019-0550 · Cited by 57
Immune Checkpoint Inhibitors in the Management of Lung Cancer
Zimmermann, S., Peters, S., Owinokoko, T., & Gadgeel, S. M. (2018) · American Society of Clinical Oncology Educational Book · doi:10.1200/edbk_201319 · Cited by 59
Kim, K. H., Hur, J. Y., Cho, J., Ku, B. M., Koh, J., Koh, J., Sun, J., Lee, S., Ahn, J. S., Park, K., et al. (2020) · OncoImmunology · doi:10.1080/2162402x.2020.1722023 · Cited by 60
Valencia-Sánchez, C., & Ζεκερίδου, Α. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2021.642800 · Cited by 58
“Exacerbation of Pre-existing Autoimmunity ICI treatment may unmask latent autoimmunity, in patients with underlying autoimmunity that remained subclinical before ICI treatment (43, 47).”
BackgroundZhan, L., Feng, H.-F., Liu, H., Guo, L., Chen, C., Yao, X.-L., & Sun, S. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.649863 · Cited by 62
Current and future immunotherapies for thyroid cancer
Antonelli, A., Ferrari, S. M., & Fallahi, P. (2017) · Expert Review of Anticancer Therapy · doi:10.1080/14737140.2018.1417845 · Cited by 59
Targeting immune checkpoints in non small cell lung cancer
Bianco, A., Malapelle, U., Rocco, D., Perrotta, F., & Mazzarella, G. (2018) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2018.02.006 · Cited by 57
Emerging Management Approach for the Adverse Events of Immunotherapy of Cancer
Rahman, M. M., Behl, T., Islam, M. R., Islam, M. R., Islam, M. R., Albarrati, A., Albratty, M., Meraya, A. M., & BUNGAU, S. G. (2022) · Molecules · doi:10.3390/molecules27123798 · Cited by 55
“In cases like these, ICPis treatment should be stopped once no improvement has been seen as a result of these therapies until a dermatologist can determine if there is a hope of healing [96,97].”
BackgroundUbiquitin Ligases in Cancer Immunotherapy – Balancing Antitumor and Autoimmunity
Fujita, Y., Tinoco, R., Li, Y., Senft, D., & Ronai, Z. A. (2019) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2019.02.002 · Cited by 55
Riudavets, M., Mosquera, J., García‐Campelo, R., Serra-López, J., Anguera, G., Gallardo, P., Sullivan, I., Joaquín, A. B., del Carpio, L. P., Barnadas, A., et al. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.01677 · Cited by 55
“Consistent with our findings, two studies have also suggested that thyroiditis and skin toxicity are related to longer OS (32, 33).”
ResultUsing Combination therapy to overcome diverse challenges of Immune Checkpoint Inhibitors treatment
Birnboim-Perach, R., & Benhar, I. (2024) · International Journal of Biological Sciences · doi:10.7150/ijbs.93697 · Cited by 58
“While the pathogenic role of T cells in irAEs is well-established, emerging evidence suggests a contribution from B cells as well 87,88 .”
BackgroundFerreira, J. L., Costa, C. F., Marques, B., Castro, S., Víctor, M., Oliveira, J., Santos, A. P., Sampaio, I. L., Duarte, H., Marques, A. P., et al. (2020) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-020-02664-y · Cited by 55
Wang, M., Liang, H., Wang, W., Zhao, S., Cai, X., Zhao, Y., Li, C., Cheng, B., Xiong, S., Li, J., et al. (2020) · Cancer · doi:10.1002/cncr.33270 · Cited by 53
“Thyroid dysfunction is the result of facilitating downstream B-cell immunoglobulin expression by a T cell–independent mechanism.(43,44) In other systems, the mechanism of infusion-related reactions has been proposed to be a combination of medicine and immunoglobulin E, which leads to the release of histamine.”
BackgroundYao, L., Jia, G., Lu, L., Bao, Y., & Ma, W. (2020) · International Immunopharmacology · doi:10.1016/j.intimp.2020.106628 · Cited by 54
Defining unique clinical hallmarks for immune checkpoint inhibitor-based therapies
Michielin, O. A., Lalani, A. A., Robert, C., Sharma, P., & Peters, S. (2022) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2021-003024 · Cited by 52
Predictive Factors of Nivolumab-induced Hypothyroidism in Patients with Non-small Cell Lung Cancer
(2018) · In Vivo · doi:10.21873/invivo.11166 · Cited by 51
“Osorio et al. (17) reported that 10 of 48 pembrolizumab-treated patients who were not hypothyroid at baseline developed thyroid dysfunction.”
BackgroundMazarico, I., Capel, I., Giménez‐Palop, O., Albert, L., Berges, I., Luchtenberg, F., García, Y. G., Fernandez-Morales, L. A., de Pedro, V. J., Caixàs, A., et al. (2019) · Journal of Endocrinological Investigation · doi:10.1007/s40618-019-01058-x · Cited by 51
Autoimmune Endocrinopathies: An Emerging Complication of Immune Checkpoint Inhibitors
Quandt, Z., Young, A., Perdigoto, A. L., Herold, K. C., & Anderson, M. S. (2020) · Annual Review of Medicine · doi:10.1146/annurev-med-050219-034237 · Cited by 53
The double-edged sword: Harnessing PD-1 blockade in tumor and autoimmunity
Kuchroo, J. R., Hafler, D. A., Sharpe, A. H., & Lucca, L. E. (2021) · Science Immunology · doi:10.1126/sciimmunol.abf4034 · Cited by 51
“Antithyroid antibodies have been reported in patients with thyroiditis after checkpoint blockade and pituitary antibodies have been found in patients with hypophysitis after anti–CTLA-4 therapy (132, 139, 140).”
BackgroundSakakida, T., Ishikawa, T., Uchino, J., Chihara, Y., Komori, S., Asai, J., Narukawa, T., Arai, A., Kobayashi, T., Tsunezuka, H., et al. (2019) · Oncology Letters · doi:10.3892/ol.2019.10466 · Cited by 50
Sugano, T., Seike, M., Saito, Y., Kashiwada, T., Terasaki, Y., Takano, N., Hisakane, K., Takahashi, S., Tanaka, T., Takeuchi, S., et al. (2020) · Thoracic Cancer · doi:10.1111/1759-7714.13364 · Cited by 50
McGregor, B. A., Mortazavi, A., Cordes, L. M., Salabao, C., Vandlik, S., & Apolo, A. B. (2021) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2021.102333 · Cited by 50
Ueda, K., Yonekura, S., Ogasawara, N., Matsunaga, Y., Hoshino, R., Kurose, H., Chikui, K., Uemura, K., Nakiri, M., Nishihara, K., et al. (2019) · Anticancer Research · doi:10.21873/anticanres.13836 · Cited by 50
Mechanisms of checkpoint inhibition-induced adverse events
Urwyler, P., Earnshaw, I., Bermudez, M., Perucha, E., Wu, W., Ryan, S. E., Mcdonald, L., Karagiannis, S. N., Taams, L. S., Powell, N., et al. (2020) · Clinical & Experimental Immunology · doi:10.1111/cei.13421 · Cited by 48
Anticancer Drug-induced Thyroid Dysfunction
Bhattacharya, S., Goyal, A., Kaur, P., Medanta, T. M., Singh, R. K., & Kalra, S. (2020) · touchREVIEWS in Endocrinology · doi:10.17925/ee.2020.16.1.32 · Cited by 50
“34 EUROPEAN ENDOCRINOLOGY the subset of subjects who developed thyroid dysfunction (8/10, 80%), compared to those who did not (3/38, 8%).(11) Similar to the ipilimumab hypophysitis study, subjects developing thyroid dysfunction had overall better survival (hazard ratio, 0.”
ResultImmune Checkpoint Inhibitor-induced Thyroid Dysfunction Is Associated with Higher Body Mass Index
Pollack, R. M., Ashash, A., Cahn, A., Rottenberg, Y., Stern, H., & Dresner–Pollak, R. (2020) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaa458 · Cited by 49
“It has also been proposed that ICI-induced thyroid dysfunction may simply be unmasking of latent autoimmunity and the presence of thyroid antibodies in up to 18% of the general population (32% of adults age 60+ years) may explain why thyroid irAEs are so common (20-22).”
BackgroundZhao, Z., Wang, X., Qu, J., Zuo, W., Tang, Y., Zhu, H., & Chen, X. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.708195 · Cited by 49
Dóra, D., Bokhari, S. M. Z., Aloss, K., Takacs, P., Desnoix, J. Z., Szklenárik, G., Hurley, P. D., & Lohinai, Z. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032769 · Cited by 48
“B cells produce auto-antibodies in response to ICI against self-reactive T and B cells [108,109] which commonly damage the thyroid and islet cells of the pancreas leading to thyroiditis, hypothyroidism and diabetes, respectively [50,110].”
Background18F-FDG PET/CT Can Predict Development of Thyroiditis Due to Immunotherapy for Lung Cancer
Eshghi, N., Garland, L. L., Nia, E. S., Betancourt, R., Krupinski, E. A., & Kuo, P. H. (2018) · Journal of Nuclear Medicine Technology · doi:10.2967/jnmt.117.204933 · Cited by 48
“The onset of hypothyroidism during therapy occurred between the third and sixth cycles of therapy, as was in line with prior published studies (25,26).”
ResultBrilli, L., Danielli, R., Campanile, M., Secchi, C., Ciuoli, C., Calabrò, L., Pilli, T., Cartocci, A., Pacini, F., Giacomo, A. M. D., et al. (2020) · Journal of Endocrinological Investigation · doi:10.1007/s40618-020-01480-6 · Cited by 50
Dupont, R., Bérard, E., Puisset, F., Comont, T., Delord, J., Guimbaud, R., Meyer, N., Mazières, J., & Alric, L. (2019) · OncoImmunology · doi:10.1080/2162402x.2019.1682383 · Cited by 47
Ksienski, D., Wai, E. S., Alex, D., Croteau, N. S., Freeman, A. T., Chan, A. M. Y., Patterson, T., Clarkson, M., Fiorino, L., Poonja, Z., et al. (2021) · Translational Lung Cancer Research · doi:10.21037/tlcr-20-541 · Cited by 46
“Risk factors for irAE amongst pembrolizumab treated aNSCLC patients have included: history of autoimmune disease (20), female gender (41), elevated BMI (42), pre-existing auto-antibodies (43,44), baseline derived NLR >3 (42), and baseline PLR <180 (23).”
Taylor, J., Gandhi, A., Gray, E. S., & Zaenker, P. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2022.991433 · Cited by 47
“(69), antithyroid antibodies were frequently found in patients who developed ICI-induced thyroid dysfunction.”
BackgroundFukushima, T., Morimoto, M., Kobayashi, S., Ueno, M., Uojima, H., Hidaka, H., Kusano, C., Chuma, M., Numata, K., Tsuruya, K., et al. (2023) · The Oncologist · doi:10.1093/oncolo/oyad090 · Cited by 46
König, D., & Laubli, H. P. (2020) · Pharmacology · doi:10.1159/000509081 · Cited by 49
Adverse Effects of Immune-Checkpoint Inhibitors in Hepatocellular Carcinoma
Cui, T., Liu, Y., Wang, J.-B., & Liu, L. (2020) · OncoTargets and Therapy · doi:10.2147/ott.s279858 · Cited by 47
Li, L., Liu, Y., Chen, C., Wei, A., & Li, W. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1190001 · Cited by 45
Iwama, S., Kobayashi, T., & Arima, H. (2025) · Nature Reviews Endocrinology · doi:10.1038/s41574-024-01077-6 · Cited by 46
“The development of thyroid irAEs was shown to be associated with prolonged overall survival in people with NSCLC treated with anti-PD1 antibodies 58–60 .”
Ksienski, D., Wai, E. S., Croteau, N. S., Freeman, A. T., Chan, A. M. Y., Fiorino, L., Brooks, E. G., Poonja, Z., Fenton, D. W., Geller, G. S., et al. (2019) · Lung Cancer · doi:10.1016/j.lungcan.2019.05.005 · Cited by 45
Current status and future perspectives of immunotherapy in bladder cancer treatment
Wu, Z., Liu, J., Dai, R., & Wu, S. (2020) · Science China Life Sciences · doi:10.1007/s11427-020-1768-y · Cited by 45
“can be explained due to the increase in pre-existing antithyroid antibodies correlated with humoral immunity (Osorio et al., 2017).”
BackgroundOkawa, S., Kayatani, H., Fujiwara, K., Ozeki, T., Takada, K., Iwamoto, Y., Minami, D., Sato, K., & Shibayama, T. (2019) · Internal Medicine · doi:10.2169/internalmedicine.1001-18 · Cited by 44
“indicated that thyroid dysfunction that can occur early in treatment is frequently preceded by transient hyperthyroidism associated with an improved outcome of pembrolizumab (13).”
BackgroundIwama, S., Kobayashi, T., Yasuda, Y., Okuji, T., Ito, M., Ando, M., Zhou, X., Yamagami, A., Onoue, T., Kawaguchi, Y., et al. (2021) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgab829 · Cited by 44
Expert opinion on thyroid complications in immunotherapy
Illouz, F., Drui, D., Caron, P. J., & Cao, C. D. (2018) · Annales d Endocrinologie · doi:10.1016/j.ando.2018.07.007 · Cited by 44
Labadie, B. W., Liu, P., Bao, R., Crist, M., Fernandes, R., Ferreira, L., Graupner, S., Poklepovic, A. S., Durán, I., Vareki, S. M., et al. (2019) · Journal of Translational Medicine · doi:10.1186/s12967-019-02144-7 · Cited by 43
Baldini, E., Lunghi, A., Cortesi, E., Turci, D., Signorelli, D., Stati, V., Melotti, B., Ricciuti, B., Frassoldati, A., Romano, G., et al. (2019) · Lung Cancer · doi:10.1016/j.lungcan.2019.12.014 · Cited by 43
Thuillier, P., Joly, C., Alavi, Z., Crouzeix, G., Descourt, R., Quéré, G., Kerlan, V., & Roudaut, N. (2021) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-020-02802-6 · Cited by 44
“Regarding TD induced by ICI, several studies reported an association between TD and response to anti-PD-1 in patients treated with pembrolizumab [14] and nivolumab [16, 17].”
BackgroundImmune Checkpoint Inhibitor-Induced Hypophysitis: Lessons Learnt from a Large Cancer Cohort
Kotwal, A., Rouleau, S. G., Dasari, S., Kottschade, L. A., Ryder, M. M., Kudva, Y. C., Markovic, S. N., & Erickson, D. Z. (2021) · Journal of Investigative Medicine · doi:10.1136/jim-2021-002099 · Cited by 43
Thyroid Dysfunctions Due to Immune Checkpoint Inhibitors: A Review
Sabbagh, R. E., Azar, N. S., Eid, A. A., & Azar, S. T. (2020) · International Journal of General Medicine · doi:10.2147/ijgm.s261433 · Cited by 45
Immunotherapy of thymic epithelial tumors: molecular understandings and clinical perspectives
Ao, Y.-Q., Gao, J., Wang, S., Jiang, J.-H., Deng, J., Wang, H., Xu, B., & Ding, J. (2023) · Molecular Cancer · doi:10.1186/s12943-023-01772-4 · Cited by 42
Campredon, P., Mouly, C., Lusque, A., Bigay-Game, L., Bousquet, E., Mazières, J., & Caron, P. J. (2019) · La Presse Médicale · doi:10.1016/j.lpm.2018.10.019 · Cited by 41
“It has been described with other anti-PD-1 monoclonal antibody (pembrolizumab) in NSCLC that patients with thyroid dysfunctions had a better overall survival than those in the group who did not develop it [16].”
BackgroundZhou, Y., Xia, R., Xiao, H., Pu, D., Long, Y., Ding, Z., Liu, J., & Ma, X. (2020) · International Immunopharmacology · doi:10.1016/j.intimp.2020.107296 · Cited by 42
Thyroid disorders induced by immune checkpoint inhibitors
Karaviti, D., Kani, E.-R., Karaviti, E., Gerontiti, E., Michalopoulou, O., Stefanaki, K., Kazakou, P., Vasileiou, V., Ψαλτοπούλου, Θ., & Paschou, S. Α. (2024) · Endocrine · doi:10.1007/s12020-024-03718-2 · Cited by 40
“In the Osorio et al. study, TPOAb and TgAb levels were examined not only at baseline, but also during pem-brolizumab (anti-PD-1) treatment [18].”
BackgroundManagement of Brain Metastases in the New Era of Checkpoint Inhibition
Lauko, A. J., Thapa, B., Venur, V. A., & Ahluwalia, M. S. (2018) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-018-0877-8 · Cited by 41
A Review of Immune-Mediated Adverse Events in Melanoma
Kennedy, L. B., & Salama, A. K. S. (2019) · Oncology and Therapy · doi:10.1007/s40487-019-0096-8 · Cited by 41
Chieng, J. H. L., Htet, Z. W., Zhao, J. J., Tai, E. S., Tay, S. H., Huang, Y., Wong, A. S. C., & Yang, S. P. (2022) · Cancers · doi:10.3390/cancers14112687 · Cited by 40
“A previous study found that the thyroid autoantibodies developed shortly after commencement of pembrolizumab and hypothesised that ICIs uncovered underlying autoimmunity by modulating the auto-immune equilibrium [25].”
BackgroundLu, D., Yao, J., Yuan, G., Gao, Y., Zhang, J., & Guo, X. (2022) · The Oncologist · doi:10.1093/oncolo/oyab043 · Cited by 38
Matsuo, N., Azuma, K., Hattori, S., Ohtake, J., Kawahara, A., Ishii, H., Tokito, T., Yamada, K., Shibata, Y., Shimokawaji, T., et al. (2018) · International Journal of Cancer · doi:10.1002/ijc.31923 · Cited by 38
Peripheral blood immune cell-based biomarkers in anti-PD-1/PD-L1 therapy
Kim, K. H., Kim, C. G., & Shin, E. (2020) · Immune Network · doi:10.4110/in.2020.20.e8 · Cited by 37
“(76) demonstrated that the presence of anti-thyroid Abs at baseline or during anti-PD-1 treatment is significantly associated with thyroid dysfunction after treatment in NSCLC patients.”
BackgroundDadu, R., Rodgers, T. E., Trinh, V. A., Kemp, E. H., Cubb, T. D., Patel, S. P., Simon, J. M., Burton, E. M., & Tawbi, H. A. (2020) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-000687 · Cited by 38
Iwama, S., Kobayashi, T., & Arima, H. (2021) · Endocrinology and Metabolism · doi:10.3803/enm.2021.1007 · Cited by 38
Endocrine-related adverse events in a large series of cancer patients treated with anti-PD1 therapy
Rubino, R., Marini, A., Roviello, G., Presotto, E. M., Desideri, I., Ciardetti, I., Brugia, M., Pimpinelli, N., Antonuzzo, L., Mini, E., et al. (2021) · Endocrine · doi:10.1007/s12020-021-02750-w · Cited by 37
Mechanism‐based treatment of cancer with immune checkpoint inhibitor therapies
Abdou, Y. G., Pandey, M. R., Sarma, M., Shah, S., Baron, J. I., & Ernstoff, M. S. (2020) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.14316 · Cited by 35
von Itzstein, M. S., Gonugunta, A. S., Wang, Y., Sheffield, T. Y., Lü, R., Ali, S., Fattah, F. J., Xie, D., Cai, J. X., Xie, Y., et al. (2022) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-022-03151-2 · Cited by 36
“As observed with other irAE [15–17], the occurrence of ICI-induced thyroid dysfunction appears associated with improved clinical outcomes [18, 19], an observation that may reflect cross-reactivity between anti-tumor and autoimmune responses or even germline genetic factors [20, 21].”
BackgroundResultZhou, X., Iwama, S., Kobayashi, T., Ando, M., & Arima, H. (2023) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgad231 · Cited by 35
Uncoupling Therapeutic Efficacy from Immune-Related Adverse Events in Immune Checkpoint Blockade
Hu, W., Wang, G., Wang, Y., Riese, M. J., & You, M. (2020) · iScience · doi:10.1016/j.isci.2020.101580 · Cited by 35
HLA and tumour immunology: immune escape, immunotherapy and immune-related adverse events
Jiang, N., Yu, Y., Wu, D., Wang, S., Fang, Y., Miao, H., Ma, P., Huang, H., Zhang, M., Zhang, Y. X., et al. (2023) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-022-04493-1 · Cited by 35
Cooksley, T., Girotra, M., Ginex, P., Gordon, R. A., Anderson, R., Blidner, A. G., Choi, J. N., Dougan, M. L., Glezerman, I. G., Gupta, D., et al. (2020) · Supportive Care in Cancer · doi:10.1007/s00520-020-05709-1 · Cited by 34
Sbardella, E., Tenuta, M., Sirgiovanni, G., Gianfrilli, D., Pozza, C., Venneri, M. A., Cortesi, E., Marchetti, P., Lenzi, A., Gelibter, A. J., et al. (2019) · Clinical Endocrinology · doi:10.1111/cen.14135 · Cited by 34
Immune Checkpoint Inhibitors in the Treatment of Renal Cell Carcinoma
Parikh, M., & Bajwa, P. (2020) · Seminars in Nephrology · doi:10.1016/j.semnephrol.2019.12.009 · Cited by 33
Li, Y., Li, C., Guo, S., Guo, W., Jiang, H., Li, H., & Tao, S. (2020) · EBioMedicine · doi:10.1016/j.ebiom.2020.102674 · Cited by 33
“The level of autoantibodies increased after cancer treatment are barely reported except for the antigens related to autoimmune diseases for immunotherapy [5,20] or tumor associated antigens for chemotherapy [17,19].”
BackgroundLondoño, M., Reig, M., & on behalf of the RETOINMUNO Multidisciplinary Group (2020) · Cancers · doi:10.3390/cancers12113446 · Cited by 34
“Moreover, endocrine toxicity seems to be correlated with the efficacy of ICPI and a higher survival rate, but the evidence on this issue is still limited [50,51].”
BackgroundMosaferi, T., Tsai, K., Sovich, S., Wilhalme, H. M., Kathuria‐Prakash, N., Praw, S. S., Drakaki, A., Angell, T. E., & Lechner, M. G. (2022) · Thyroid · doi:10.1089/thy.2021.0685 · Cited by 36
“Finally, our study was specifically focused on ICI-associated thyroiditis, defined as a period of ICI-induced initial hyperthyroidism that transitions to hypo-thyroidism (8,17,23).”
Graves’ Disease during Immune Checkpoint Inhibitor Therapy (A Case Series and Literature Review)
Peiffert, M., Cugnet-Anceau, C., Dalle, S., Chikh, K., Assaad, S., Disse, E., Raverot, G., Borson-Chazot, F., & Abeillon-du Payrat, J. (2021) · Cancers · doi:10.3390/cancers13081944 · Cited by 33
“Note that in the Osorio study [56], survival was better if patients developed ICPi-induced thyroid dysfunction, as suggested by others if there was an occurrence of irAEs [58–60].”
BackgroundNivolumab Induced Thyroid Dysfunction: Unusual Clinical Presentation and Challenging Diagnosis
Iadarola, C., Croce, L., Quaquarini, E., Teragni, C., Pinto, S., Bernardo, A., Fonte, R., Marinò, M., Rotondi, M., & Chiovato, L. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00813 · Cited by 33
“Indeed, some studies report a close relationship between thyroid antibodies and PD-1 inhibitor-induced thyroid dysfunction (13) while others do not (14, 15).”
BackgroundLópez-Guerra, N., Matas-García, A., Serra‐García, L., Morgado‐Carrasco, D., Padrosa, J., Aldecoa, I., Duque-Jaimez, Y., Casal-Domínguez, M., Muñoz-Braceras, S., Aránega, R., et al. (2023) · Autoimmunity Reviews · doi:10.1016/j.autrev.2023.103375 · Cited by 33
Seban, R., Arnaud, E., Loirat, D., Cabel, L., Cottu, P. H., Djerroudi, L., Hescot, S., Loap, P., Bonneau, C., Bidard, F., et al. (2023) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-023-06394-y · Cited by 35
“However, the presence of thyroid antibodies does not predict hypothyroidism either and is observed in less than half of patients who develop ICI-induced hypothyroidism [39].”
BackgroundImmune Checkpoint Inhibitors in Clear Cell Renal Cell Carcinoma (ccRCC)
Rysz, J., Ławiński, J., Franczyk, B., & Gluba-Brzózka, A. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26125577 · Cited by 36
“However, this immune stimulation may also lead to the recognition of self-antigens or the exacerbation of subclinical inflammation, resulting in irAEs such as endocrine dysfunctions, hepatotoxicity, colitis, and elevations in pancreatic enzymes [96–99].”
Fiala, O., Šorejs, O., Šustr, J., Kučera, R., Topolčan, O., & Fínek, J. (2020) · Anticancer Research · doi:10.21873/anticanres.14063 · Cited by 34
Li, Q., Cao, M., Yuan, G., Cheng, X., Zang, M., Chen, M., Hu, X., Huang, J., Li, R., Guo, Y., et al. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.809709 · Cited by 33
Wu, L., Xu, Y., Wang, X., Cheng, X., Zhang, Y., Wang, Y., Fan, X., Zhao, H., Liu, H., Chai, X., et al. (2023) · Endocrine · doi:10.1007/s12020-023-03323-9 · Cited by 33
Metadata
- Authors
- Osorio, J. C., Ni, A., Chaft, J. E., Pollina, R., Kasler, M. K., Stephens, D., Rodriguez, C., Cambridge, L., Rizvi, H., Wolchok, J. D., Merghoub, T., Rudin, C. M., Fish, S., & Hellmann, M. D.
- Affiliations
- Weill Cornell Medicine (US)
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Hellmann, M.D.
- Venue
- Annals of Oncology
- Publisher
- Elsevier BV
- Published
- 2017-03
- Volume
- 28
- Issue
- 3
- Pages
- 583-589
- ISSN
- 0923-7534 (ISSN-L)
- PMC
- PMC5834017
- OpenAlex
- W2561156916
- Cited by
- 659
- References
- 26
- Citations by year
- 2026: 23 · 2025: 50 · 2024: 70 · 2023: 75 · 2022: 102 · 2021: 95 · 2020: 98 · 2019: 77 · 2018: 51 · 2017: 17
- FWCI
- 26.03
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Annals of Oncology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (P30 CA008748)
- Fiona and Stanley Druckenmiller Center for Lung Cancer Research
- KEYNOTE-001 (NCT01295827)
- Merck Sharp & Dohme, a subsidiary of Merck
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Clinical Neurology › Autoimmune Neurological Disorders and Treatments
- Keywords
- immune-related adverse events, anti-thyroid antibodies, pembrolizumab, anti-PD-1 therapy, non-small cell lung cancer, hypothyroidism, hyperthyroidism, humoral immunity, immune checkpoint inhibitors, progression-free survival, overall survival
- MeSH terms
- Adolescent, Adult, Aged, Antibodies, Monoclonal, Carcinoma, Non-Small-Cell Lung, Female, Humans, Hyperthyroidism, Male, Middle Aged, Neoplasm Staging, T-Lymphocytes, Thyroid Gland, Disease-Free Survival, Programmed Cell Death 1 Receptor, Antibodies, Monoclonal, Humanized, Drug-Related Side Effects and Adverse Reactions
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