The DOI matches its Crossref record; 25 of the 26 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“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]
The cited source says what the claim attributes to it.
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
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
Flagged first, then by citations
1 of the 26 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Items 201–300 of 659
Thyroxine promotes lung cancer growth in an orthotopic mouse model
Latteyer, S., Christoph, S., Theurer, S., Hönes, G. S., Schmid, K. W., Führer, D., & Moeller, L. C. (2019) · Endocrine-Related Cancer · doi:10.1530/erc-18-0353 · Cited by 31
Immune checkpoint inhibitor–associated hypercalcaemia
Izzedine, H., Chazal, T., Wanchoo, R., & Jhaveri, K. D. (2020) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfaa326 · Cited by 32
Chen, X., Nie, J., Dai, L., Hu, W., Zhang, J., Han, J., Ma, X., Tian, G., Han, S., Wu, D., et al. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.607531 · Cited by 32
Endocrine immune-related adverse events: Adrenal, parathyroid, diabetes insipidus, and lipoatrophy
Atkinson, M. A., & Lansdown, A. (2022) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2022.101635 · Cited by 32
PD-1/PD-L1 Inhibitors in Patients With Preexisting Autoimmune Diseases
Zhang, K., Kong, X., Li, Y., Wang, Z., Zhang, L., & Xuan, L. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.854967 · Cited by 34
Zhao, J., Li, D., Xie, S., Deng, X., Wen, X., Li, J., Wu, Z., Yang, X., Li, M., Tang, Y., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1083840 · Cited by 33
Achilles’ Heel of currently approved immune checkpoint inhibitors: immune related adverse events
Yan, T., Yu, L., Zhang, J., Chen, Y., Fu, Y., Tang, J., & Liao, D. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1292122 · Cited by 39
“When rechallenging with ICIs, it is of utmost importance to closely monitor the reemergence of the initial irAEs (218), as well as the patient ’ s tumor response status.”
BackgroundBest practices in the management of thyroid dysfunction induced by immune checkpoint inhibitors
Yamauchi, I., & Yabe, D. (2025) · European Thyroid Journal · doi:10.1530/etj-24-0328 · Cited by 35
Peravali, M., Gomes-Lima, C. J., Tefera, E. A., Baker, M., Sherchan, M., Farid, S., Burman, K. D., Constantinescu, F., & Veytsman, I. G. (2021) · World Journal of Clinical Oncology · doi:10.5306/wjco.v12.i2.103 · Cited by 31
Exploiting the obesity-associated immune microenvironment for cancer therapeutics
Desharnais, L., Walsh, L. A., & Quail, D. F. (2021) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.107923 · Cited by 31
Labadzhyan, A., Wentzel, K. P., Hamid, O., Chow, K., Kim, S., Piro, L. D., & Melmed, S. K. (2022) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgac161 · Cited by 31
Autoimmune polyendocrine syndrome induced by immune checkpoint inhibitors: A systematic review
Zhao, Z., Wang, X., Bao, X.-Q., Ning, J., Shang, M., & Zhang, D. (2021) · Cancer Immunology, Immunotherapy · doi:10.1007/s00262-020-02699-1 · Cited by 30
Clinical Characters and Influence Factors of Immune Checkpoint Inhibitor-related Thyroid Dysfunction
Zhang, Q., Jiao, X., & Lai, X. (2023) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgad260 · Cited by 31
Ponvilawan, B., Khan, A. W., Subramanian, J., & Bansal, D. (2024) · Cancers · doi:10.3390/cancers16061225 · Cited by 33
“Inter-estingly, a cohort of patients with NSCLC who received pembrolizumab and developed hypothyroid irAEs exhibited a common thyroid function trajectory of initial transient hyperthyroidism within 1–2 months after pembrolizumab therapy, followed by prolonged hypothyroidism [93].”
BackgroundTwo distinct clinical patterns of checkpoint inhibitor-induced thyroid dysfunction
Olsson-Brown, A. C., Lord, R., Sacco, J. J., Wagg, J., Coles, M. C., & Pirmohamed, M. (2020) · Endocrine Connections · doi:10.1530/ec-19-0473 · Cited by 32
“…trials (Supplementary Table 1) the predominant pattern of toxicity was hyperthyroidism transient thyroiditis has been previously identified (13, 17); however, with regular patient sampling throughout treatment with ICIs, we have illustrated that the majority of patients actually experience…”
Yura, Y., & Hamada, M. (2022) · Cancers · doi:10.3390/cancers14030792 · Cited by 33
“Autoantibodies against thyroid antigens are detectable in ICIrelated thyroiditis and hypothyroidism [60].”
BackgroundBaek, H.-S., Jeong, C., Shin, K., Lee, J., Suh, H., Lim, D., Kang, M. I., & Ha, J. (2022) · BMC Endocrine Disorders · doi:10.1186/s12902-022-01004-8 · Cited by 30
“Similar results have been reported extensively [26, 27, 29, 30].”
Mushref, M. A., Guido, P., Collichio, F. A., Moore, D. T., & Clemmons, D. R. (2019) · Endocrine Practice · doi:10.4158/ep-2019-0244 · Cited by 29
Li, B., Jiang, C., Pang, L., Zou, B., Ding, M., Sun, X., Yu, J., & Wang, L. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.627197 · Cited by 30
Giommoni, E., Giorgione, R., Paderi, A., Pellegrini, E., Gambale, E., Marini, A., Antonuzzo, A., Marconcini, R., Roviello, G., Matucci‐Cerinic, M., et al. (2021) · Immuno · doi:10.3390/immuno1030017 · Cited by 30
Paraneoplastic Autoimmune Neurological Syndromes and the Role of Immune Checkpoint Inhibitors
Duong, S. L., & Prüss, H. (2022) · Neurotherapeutics · doi:10.1007/s13311-022-01184-0 · Cited by 29
“Another possible pathogenic mechanism of neurologic irAEs is the modulation of humoral immunity with increased B cell-mediated antibody production [30].”
Lu, L., Xing, K., Wei, W., Ling, Y., Li, P., Li, S., Wang, Y., Xie, D., Guo, R., & Cai, M. (2021) · International Journal of Cancer · doi:10.1002/ijc.33609 · Cited by 28
Complications following novel therapies for non‐small cell lung cancer
Skribek, M., Rounis, K., Tsakonas, G., & Ekman, S. (2022) · Journal of Internal Medicine · doi:10.1111/joim.13445 · Cited by 28
Nasca, V., Barretta, F., Corti, F., Lonardi, S., Niger, M., Élez, E., Fakih, M., Jayachandran, P., Shah, A. T., Salati, M., et al. (2023) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2022-005493 · Cited by 29
Percik, R., Criseno, S., Adam, S., Young, K., & Morganstein, D. L. (2023) · Endocrine Connections · doi:10.1530/ec-22-0513 · Cited by 28
Spagnuolo, A., & Gridelli, C. (2018) · Journal of Thoracic Disease · doi:10.21037/jtd.2018.09.83 · Cited by 28
“There is recent evidence that the onset of irAEs may be linked to a response to ICIs and to longer survival in NSCLC patients (9-13), although studies”
BackgroundHwang, S. W., Kim, M. K., & Kweon, M. (2023) · Intestinal Research · doi:10.5217/ir.2023.00019 · Cited by 28
“For example, anti-PD-1 or anti-PD-L1 treatment may enhance antithyroid antibodies in patients developing thyroiditis.(47) Other autoantibodies produced in response to ICI therapy have been identified, including autoantibodies to thyrotropin, follicle-stimulating hormone, and corticotropin-secreting cells in patients d…”
BackgroundDelire, B., Martin, E. D., Meunier, L., Larrey, D. G., & Horsmans, Y. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.786174 · Cited by 28
“In contrast, patients treated with anti–PD-1 can have antithyroid antibodies detected both before and after therapy initiation, suggesting that ICIs can also enhance preexisting antithyroid antibodies (Osorio et al., 2017).”
Shalit, A., Sarantis, P., Koustas, E., Trifylli, E.-M., Matthaios, D., & Karamouzis, M. V. (2023) · Cancers · doi:10.3390/cancers15020375 · Cited by 29
“Terms such as “pituitary dysfunction”, “hypophysitis”, and “hypopituitarism” are mainly used interchangeably but sometimes as separate entities; “isolated adrenocorticotropin insufficiency” is similarly examined as a part of pituitary dysfunction or separately [43,78,79], and thyroid dysfunction may represent only ove…”
BackgroundScarpelli, M., Zahm, C. D., Perlman, S. B., McNeel, D. G., Jeraj, R., & Liu, G. (2019) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-019-0516-1 · Cited by 27
“A previous study suggested PD-1 blockade may cause latent thyroid auto-immunity to become clinically detectable and lead to subsequent thyroid-related adverse events [48].”
BackgroundGómez-Banoy, N., Ortiz, E. J., Jiang, C. S., Dagher, C., Sevilla, C., Girshman, J., Pagano, A., Plodkowski, A. J., Zammarrelli, W. A., Mueller, J. J., et al. (2024) · Journal of Clinical Investigation · doi:10.1172/jci180516 · Cited by 30
“Previous studies suggest a positive association between improved clinical responses to ICI and development of irAEs (31–34).”
ResultWu, Z., Huang, R., Sun, W., He, B., & Wang, C. (2024) · Archives of Dermatological Research · doi:10.1007/s00403-024-03484-1 · Cited by 26
“Another possible mecha - nism is that PD-1/PD-L1 inhibitors may modulate humoral immunity which enhances pre-existing autoantibodies and unmask latent auto-immunity [ 26, 27].”
Bouhlel, L., Doyen, J., Chamorey, E., Poudenx, M., Ilié, M., Gal, J., Guigay, J., Benzaquen, J., Marquette, C., Berthet, J., et al. (2020) · Bulletin du Cancer · doi:10.1016/j.bulcan.2020.04.019 · Cited by 26
Kijima, T., Fukushima, H., Kusuhara, S., Tanaka, H., Yoshida, S., Yokoyama, M., Ishioka, J., Matsuoka, Y., Numao, N., Sakai, Y., et al. (2020) · Clinical Genitourinary Cancer · doi:10.1016/j.clgc.2020.07.003 · Cited by 26
Endocrine toxicity of cancer immunotherapy: clinical challenges
Anderson, B., & Morganstein, D. L. (2021) · Endocrine Connections · doi:10.1530/ec-20-0489 · Cited by 26
Shimozaki, K., Sukawa, Y., Sato, Y., Horie, S., Chida, A., Tsugaru, K., Togasaki, K., Kawasaki, K., Hirata, K., Hayashi, H., et al. (2021) · Future Oncology · doi:10.2217/fon-2020-0861 · Cited by 27
Li, Y.-L., Zhang, Y., Jia, X., Jiang, P., Mao, Z., Liang, T. B., Du, Y., Zhang, J., Zhang, G., Niu, G., et al. (2021) · Clinical Lung Cancer · doi:10.1016/j.cllc.2021.05.004 · Cited by 26
Bardoscia, L., Pasinetti, N., Triggiani, L., Cozzi, S., & Sardaro, A. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.746853 · Cited by 28
Immune-Related Toxicity in NSCLC: Current State-of-the-Art and Emerging Clinical Challenges
O’Leary, C. L., Pierce, N., Patel, S. P., & Naidoo, J. (2023) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2023.11.018 · Cited by 27
Check point inhibitors and autoimmunity: Why endocrinopathies and who is prone to?
Percik, R., & Shoenfeld, Y. (2020) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2020.101411 · Cited by 26
Khan, S., von Itzstein, M. S., Lü, R., Bermas, B. L., Karp, D. R., Khan, S. A., Fattah, F. J., Park, J. Y., Saltarski, J. M., Gloria-McCutchen, Y., et al. (2020) · The Oncologist · doi:10.1634/theoncologist.2019-0666 · Cited by 26
Sumimoto, H., Noda, S., Koide, H., Douke, Y., Sakai, K., Nishikawa, A., Tomioka, A., Hori, M., Nakato, H., Kimura, Y., et al. (2024) · PLoS ONE · doi:10.1371/journal.pone.0306995 · Cited by 25
Trontzas, I. P., & Syrigos, K. N. (2025) · Cancers · doi:10.3390/cancers17162639 · Cited by 27
“Furthermore, ICIs can induce a de novo development of autoantibodies during treat-ment, often preceding the onset of irAEs [87,88].”
Immune checkpoint inhibitors and endocrine side effects, a narrative review
Agrawal, L., Bacal, A., Jain, S., Singh, V., Emanuele, N. V., Emanuele, M. A., & Meah, F. A. (2019) · Postgraduate Medicine · doi:10.1080/00325481.2019.1709344 · Cited by 26
“Modulation of humoral immunity may cause an increase in the level of preexisting antibodies [16].”
BackgroundKubo, T., Hirohashi, Y., Tsukahara, T., Kanaseki, T., Murata, K., Morita, R., & Torigoe, T. (2021) · Immunological Medicine · doi:10.1080/25785826.2021.1976942 · Cited by 25
Zhang, Q., Wang, W., Yuan, Q., Li, L., Wang, Y.-C., Chi, C., & Xu, C. (2021) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-021-04375-2 · Cited by 25
“The investigators hypothesized that thyroid toxicity occur because of either humoral immunity or deterioration of low-level autoimmunity during anti-PD-1/PD-L1 antibody therapy [13].”
BackgroundRole of B cells in immune‐related adverse events following checkpoint blockade
Dhodapkar, K. M., Duffy, A. M., & Dhodapkar, M. V. (2023) · Immunological Reviews · doi:10.1111/imr.13238 · Cited by 27
Koyama, J., Horiike, A., Yoshizawa, T., Dotsu, Y., Ariyasu, R., Saiki, M., Sonoda, T., Uchibori, K., Nishikawa, S., Kitazono, S., et al. (2019) · Journal of Thoracic Disease · doi:10.21037/jtd.2019.04.102 · Cited by 23
Fatal Autoimmune Storm After a Single Cycle of Anti-PD-1 Therapy
Fuentes‐Antrás, J., Peinado, P., Guevara‐Hoyer, K., del Arco, C. D., Sánchez‐Ramón, S., & Aguado, C. (2020) · Hematology/Oncology and Stem Cell Therapy · doi:10.1016/j.hemonc.2020.04.006 · Cited by 24
Anderson, M., Kurra, V., Bradley, W. R., Kilcoyne, A., Mojtahed, A., & Lee, S. I. (2020) · British Journal of Radiology · doi:10.1259/bjr.20200663 · Cited by 24
Liang, Y., Xu, H., Liu, F., Li, L., Lin, C., Zhang, Y., Wang, N., & Wang, L. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2024.1281645 · Cited by 23
Rossi, S., Castello, A., Toschi, L., & Lopci, E. (2018) · Immunotherapy · doi:10.2217/imt-2017-0187 · Cited by 23
Paschou, S. Α., Liontos, M., Eleftherakis-Papaiakovou, E., Stefanaki, K., Markellos, C., Koutsoukos, K., Zagouri, F., Ψαλτοπούλου, Θ., & Dimopoulos, M. A. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.847917 · Cited by 23
Lu, D., Yao, J., Yuan, G., Gao, Y., Zhang, J., & Guo, X. (2022) · Journal of Endocrinological Investigation · doi:10.1007/s40618-022-01845-z · Cited by 23
Lee, S., Lee, S., Cho, H., Min, K., Hong, J. H., Song, J. Y., Lee, J. K., & Lee, N. W. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24020974 · Cited by 23
“also showed that autoantibodies are associated with hypothyroidism and pituitary inflammation induced by ICI treatment [87].”
BackgroundLin, X., Xie, M., Yao, J., Ma, X., Lin, Q., Zhang, X., Song, J., Bao, X., Zhang, X., Zhang, Y., et al. (2024) · Clinical and Translational Medicine · doi:10.1002/ctm2.1613 · Cited by 24
Music, M., Iafolla, M. A. J., Soosaipillai, A. R., Batruch, I., Prassas, I., Pintilie, M., Hansen, A. R., Bedard, P. L., Lheureux, S., Spreafico, A., et al. (2020) · F1000Research · doi:10.12688/f1000research.22715.1 · Cited by 22
Yao, J., Wang, Z., Sheng, J., Wang, H., You, L., Zhu, X., Pan, H., & Han, W. (2020) · International Immunopharmacology · doi:10.1016/j.intimp.2020.107033 · Cited by 22
Nashed, A., Zhang, S., Chiang, C.-W., Zitu, M., Otterson, G. A., Presley, C. J., Kendra, K., Patel, S. H., Johns, A., Li, M., et al. (2021) · Cancer Immunology, Immunotherapy · doi:10.1007/s00262-021-02880-0 · Cited by 22
D’Aiello, A., Lin, J., Gucalp, R. A., Tabatabaie, V., Cheng, H., Bloomgarden, N. A., Tomer, Y., & Halmos, B. (2021) · Cancers · doi:10.3390/cancers13061464 · Cited by 23
“Similarly, treatment outcomes were also not associated with thyroid dysfunction, despite previously reported associations [13,26,27].”
BackgroundResultInfluentialDeligiorgi, M. V., Sagredou, S., Vakkas, L., & Trafalis, D. T. (2021) · Cancers · doi:10.3390/cancers13215277 · Cited by 22
“[101] 51 patients with advanced NSCLC treated with pembrolizumab at Memorial Sloan Kettering Cancer Center as part of KEYNOTE-001 (NCT01295827).”
BackgroundAjgal, Z. C., Goulvestre, C., Zaibet, S., Arrondeau, J., Bretagne, M., Peyromaure, M., Batteux, F., Alexandre, J., Goldwasser, F., & Huillard, O. (2022) · Clinical Genitourinary Cancer · doi:10.1016/j.clgc.2022.04.002 · Cited by 22
Zhang, Y., Li, J., Yang, F., Zhang, X., Ren, X., & Wei, F. (2022) · Journal of Leukocyte Biology · doi:10.1002/jlb.5ma0322-746r · Cited by 23
Zhang, D., Shi, Y., Liu, X., Liu, J., Xu, Y., Zhao, J., Zhong, W., Käsmann, L., Hakozaki, T., Provencio, M., et al. (2022) · Translational Lung Cancer Research · doi:10.21037/tlcr-22-464 · Cited by 22
“Furthermore, previous studies indicated that preexisting anti-thyroglobulin (ATG) and anti-thyroid peroxidase (ATPO) were more common among patients receiving ICIs who subsequently developed thyroid dysfunction (15,16).”
Kobayashi, T., Iwama, S., Yamagami, A., Yasuda, Y., Okuji, T., Ito, M., Zhou, X., Ando, M., Onoue, T., Miyata, T., et al. (2022) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgac467 · Cited by 22
Adverse Effects of Immune-Checkpoint Inhibitors: A Comprehensive Imaging-Oriented Review
Mallio, C. A., Bernetti, C., Cea, L., Buoso, A., Stiffi, M., Vertulli, D., Greco, F., & Zobel, B. B. (2023) · Current Oncology · doi:10.3390/curroncol30050355 · Cited by 23
“Hypothyroidism, determined by destructive thyroiditis, is the most frequent manifestation, happening in 30–40% of anti-PD-1/PD-L1 induced cases [67].”
BackgroundCao, T., Zhou, X., Wu, X., & Zou, Y. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1207544 · Cited by 24
Garon-Czmil, J., Petitpain, N., Rouby, F., Sassier, M., Babai, S., Yelehe‐Okouma, M., Weryha, G., Klein, M., & Gillet, P. (2018) · Fundamental and Clinical Pharmacology · doi:10.1111/fcp.12423 · Cited by 23
Immune checkpoint inhibitor‐related type 1 diabetes incidence, risk, and survival association
Kamitani, F., Nishioka, Y., Koizumi, M., Nakajima, H., Kurematsu, Y., Okada, S., Kubo, S., Myojin, T., Noda, T., Imamura, T., et al. (2024) · Journal of Diabetes Investigation · doi:10.1111/jdi.14362 · Cited by 23
Patient-Centered Diabetes Care of Cancer Patients
Kotwal, A., Cheung, Y.-M. M., Cromwell, G. E., Drincic, A., Leblebjian, H., Quandt, Z., Rushakoff, R. J., & McDonnell, M. E. (2021) · Current Diabetes Reports · doi:10.1007/s11892-021-01435-y · Cited by 23
Safety of salvage lung resection after immunotherapy for unresectable non-small cell lung cancer
Ueno, T., Yamashita, M., Yamashita, N., Uomoto, M., Kawamata, O., Sano, Y., Inokawa, H., Hirayama, S., Okazaki, M., & Toyooka, S. (2022) · General Thoracic and Cardiovascular Surgery · doi:10.1007/s11748-022-01798-3 · Cited by 21
“There is also a risk of adrenal insufficiency and transient hyperthyroidism in the perioperative period [7].”
BackgroundBaseline risk factors associated with immune related adverse events and atezolizumab
Madjar, K., Mohindra, R., Durán-Pacheco, G., Rasul, R., Essioux, L., Maiya, V., & Chandler, G. S. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1138305 · Cited by 21
Miao, Y., Quan, W., Tang, X., Shi, W., Li, Q., Li, R. J., Wang, J., Gan, J., Dong, X., Liang, H., et al. (2024) · International Journal of Biological Sciences · doi:10.7150/ijbs.89376 · Cited by 23
“The ICIs-associated thyroid dysfunction is mostly characterized by hyperthyroidism, hypothyroidism, and/or thyroiditis [106-108].”
Yu, Y., Chen, N., Yu, S., Shen, W., Zhai, W., Li, H., & Fan, Y. (2024) · Cancer Research and Treatment · doi:10.4143/crt.2023.1118 · Cited by 21
Matsuura, N., Koh, G., Konishi, C., Minamino, S., Takahara, Y., Harada, H., Kodama, K., & Emoto, M. (2018) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-018-2203-3 · Cited by 21
Remón, J., Reguart, N., Auclin, É., & Besse, B. (2019) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2019.02.031 · Cited by 21
Clinical burden of immune checkpoint inhibitor-induced pneumonitis
Sakamoto, K., Fukihara, J., Morise, M., & Hashimoto, N. (2020) · Respiratory Investigation · doi:10.1016/j.resinv.2020.05.008 · Cited by 21
Yamauchi, I., Taura, D., Hakata, T., Fujita, H., Okamoto, K., Ueda, Y., Fujii, T., & Inagaki, N. (2020) · Clinical Endocrinology · doi:10.1111/cen.14349 · Cited by 21
Treatment of Complications from Immune Checkpoint Inhibition in Patients with Lung Cancer
Wills, B., Brahmer, J. R., & Naidoo, J. (2018) · Current Treatment Options in Oncology · doi:10.1007/s11864-018-0562-9 · Cited by 20
Role of Exosomes in Immunotherapy of Hepatocellular Carcinoma
Tian, B., Han, C., Dong, Z., Tan, S., Wang, D., & Li, T. (2022) · Cancers · doi:10.3390/cancers14164036 · Cited by 20
Jiang, C. Y., Zhao, L., Green, M. D., Ravishankar, S., Towlerton, A. M. H., Scott, A. J., Raghavan, M., Cusick, M. F., Warren, E. H., & Ramnath, N. (2024) · Scientific Reports · doi:10.1038/s41598-023-48546-y · Cited by 20
Effects of immune checkpoint inhibitor associated endocrinopathies on cancer survival
Yang, L. Y., Murthy, S., Cortellini, A., Lim, E., Gonzalez, M., Pinato, D. J., Abdel-Malek, M., Mahmoud, S., & Martin, N. M. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1369268 · Cited by 22
“Overall survival according to cancer subtype is shown in Supplementary Figure 1 (NSCLC) and Supplementary Table 1, showing a survival bene fi t in the NSCLC subgroup associated with endocrine irAEs and thyroid irAEs, but not non-endocrine irAEs.”
BackgroundInfluentialGokozan, H. N., Friedman, J. D., Schmaier, A. H., Downes, K. A., Farah, L. A., & Reeves, H. M. (2019) · Clinical Lung Cancer · doi:10.1016/j.cllc.2019.06.022 · Cited by 20
Imaging of Adverse Events Related to Checkpoint Inhibitor Therapy
Vani, V., Regge, D., Cappello, G., Gabelloni, M., & Neri, E. (2020) · Diagnostics · doi:10.3390/diagnostics10040216 · Cited by 20
Les, Í., Pérez-Francisco, I., Cabero, M., Sánchez, C., Hidalgo, M., Teijeira, L., Arrazubi, V., Domínguez, S., Anaut, P., Eguiluz, S., et al. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.894550 · Cited by 19
“For instance, the risk of developing nivolumabdestructive thyroiditis is known to be significantly higher in patients with pre-treatment anti-thyroid antibodies (namely, anti-peroxidase and anti-thyroglobulin antibodies) (Osorio et al., 2017; Kobayashi et al., 2018; Basak et al., 2020).”
BackgroundYamagata, S., Kageyama, K., Takayasu, S., Asari, Y., Makita, K., Terui, K., & Daimon, M. (2019) · Internal Medicine · doi:10.2169/internalmedicine.3008-19 · Cited by 19
Conde‐Estévez, D., Monge‐Escartín, I., Ríos-Hoyo, A., Monzonís, X., Echeverría-Esnal, D., Moliner, L., Durán, X., Taus, Á., & Arriola, E. (2020) · Journal of Chemotherapy · doi:10.1080/1120009x.2020.1849488 · Cited by 19
Ono, K., Ono, H., Toi, Y., Sugisaka, J., Aso, M., Saito, R., Kawana, S., Aiba, T., Odaka, T., Matsuda, S., et al. (2021) · Cancer Medicine · doi:10.1002/cam4.4045 · Cited by 19
Sibille, A., Alfieri, R., Malaise, O., Detrembleur, N., Pirotte, M., Louis, R. E., & Duysinx, B. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00478 · Cited by 19
Hypophysitis from immune checkpoint inhibitors: challenges in diagnosis and management
Kotwal, A. (2021) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0000000000000652 · Cited by 18
Sibille, A., Henket, M. A., Corhay, J. L., Alfieri, R., Louis, R. E., & Duysinx, B. (2021) · Lung · doi:10.1007/s00408-021-00474-2 · Cited by 19
Deligiorgi, M. V., & Trafalis, D. T. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms23010436 · Cited by 19
“[113] Prospective study of 51 patients with advanced NSCLC treated with pembrolizumab in the setting of KEYNOTE-001 (Clinical Trial Registry ID: NCT01295827).”
BackgroundHara, Y., Baba, Y., Toihata, T., Harada, K., Ogawa, K., Iwatsuki, M., Iwagami, S., Miyamoto, Y., Yoshida, N., & Baba, H. (2022) · Journal of Gastrointestinal Oncology · doi:10.21037/jgo-22-281 · Cited by 18
Basek, A., Jakubiak, G. K., Cieślar, G., & Stanek, A. (2023) · Cancers · doi:10.3390/cancers15245786 · Cited by 19
“In the study by Osario et al., among ten patients who developed thyroid dysfunction, antithyroglobulin or antimi-crosomal antibodies were found in eight patients after pembrolizumab administration [70].”
BackgroundEndocrinopathies Associated With Immune Checkpoint Inhibitor Use
Kotwal, A., Kennedy, R., Kikani, N. J., Thosani, S., Goldner, W. S., & Shariff, A. I. (2024) · Endocrine Practice · doi:10.1016/j.eprac.2024.03.023 · Cited by 20
Borgers, J. S. W., van Wesemael, T. J., Gelderman, K. A., Rispens, T., Verdegaal, E. M. E., Moes, D. J. A. R., Korse, C. M., Kapiteijn, E., Welters, M. J. P., van der Burg, S. H., et al. (2024) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2024-009215 · Cited by 22
Huang, Y., Ma, W., Wu, D., Lyu, M., Zheng, Q., Wang, T., Zhou, J., & Liu, C. (2024) · Translational Lung Cancer Research · doi:10.21037/tlcr-24-299 · Cited by 18
“Likewise, the emergence of anti-thyroid antibodies was observed to be synchronous with thyroid dysfunction following ICIs (99).”
BackgroundCascade of immunologic adverse events related to pembrolizumab treatment
Dhenin, A., Samartzi, V., Lejeune, S., & Seront, E. (2019) · BMJ Case Reports · doi:10.1136/bcr-2018-229149 · Cited by 18
Endocrine Adverse Events of Nivolumab in Non-Small Cell Lung Cancer Patients—Literature Review
Dudzińska, M., Szczyrek, M., Wojas‐Krawczyk, K., Świrska, J., Chmielewska, I., & Zwolak, A. (2020) · Cancers · doi:10.3390/cancers12082314 · Cited by 19
“The analysis of the problem is also complicated by the fact that Hashimoto’s disease affects approximately 4% of the general population and that thyroid antibodies are detected in 11% of healthy individuals [70].”
BackgroundInfluentialLin, A., Zheng, K., Jiang, A., Huang, X., Wang, Q., Hajdú, A., Li, Z., Zhang, J., & Luo, P. (2025) · Med Research · doi:10.1002/mdr2.70019 · Cited by 19
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
