Immune checkpoint inhibitors (ICIs) have generated considerable excitement as a novel class of immunotherapeutic agents due to their remarkable efficacy in treating various types of cancer. However, the widespread use of ICIs has brought about a number of safety concerns, especially the development of immune-related adverse events (irAEs). Current research hotspots are focused on how to predict irAEs that lead to treatment interruptions and the relevance of irAEs to the treatment of ICIs. irAEs, as a common complication during the treatment of ICIs, occur in approximately 40% of patients within 5 months of treatment, with thyroid disorders being among the most prevalent endocrine complications. Thyroid dysfunction manifests with a wide clinical spectrum encompassing thyroiditis, both hypo- and thyrotoxicosis, Graves’ disease. But studies have found that the occurrence and progression of irAEs is associated with survival benefits in melanoma, non-small cell lung cancer, renal cell carcinoma, and more recently in gastric cancer [19,20,21,22]. However, the association between irAEs and the prognosis of other cancers remains unknown to date [23]. Also, different irAEs presentations may exhibit different prognostic correlations, and no studies have yet shown a correlation between hypothyroidism, which is common in irAE, and tumor prognosis [24]. Therefore, studying the relationship between the development of immune thyroid dysfunction due to ICIs therapy and treatment outcome is of great clinical value for the management of patient complications and the prediction of effectiveness.

The relevance of irAEs to the prognosis of ICIs remains controversial, but some serious irAEs, include conditions like myocarditis, atherosclerosis, pericarditis, arrhythmias, and cardiomyopathy [25], which can lead to treatment interruptions and failure to respond to treatment effects. In contrast, some immune irAEs such as immune thyroiditis may be good predictors of the prognosis of ICIs.

In this study, 50 patients with different tumors treated with ICIs who developed hypothyroidism were first retrospectively analyzed, of which 30 patients developed hypothyroidism and 20 patients did not develop hypothyroidism. Analysis of the relevant baseline data showed that the age of patients who developed hypothyroidism was lower (P < 0.05), while the differences were not significant between other aspects such as gender, type of drug received, and type of tumor. Further, this study compared the treatment outcomes of patients who developed hypothyroidism with those who did not. The DCR of 30 of the hypothyroid patients was 93.3% and the ORR was 33.3%. The ORR for patients without hypothyroidism was 15.0%. The DCR and ORR of patients who developed hypothyroidism were better than those of non-hypothyroid patients, and the difference was statistically significant (P < 0.05). It proved that the treatment effect of ICIs drugs was better, and the tumor control rate was higher in patients with different tumors who developed hypothyroidism after receiving ICIs.

Further, this study analyzed the PFS data of patients treated with ICIs and demonstrated that patients with tumors receiving ICIs had better PFS, with patients who developed hypothyroidism achieving progression-free survival of 9.2 months (95% CI 7.726–10.779) and patients who did not develop a thyroid function fleet had progression-free survival of 7.3 months (95% CI 5.604–8.505). Subgroup analysis also found that PFS was 3.3 months (95% CI 0.630–5.440) for patients with cholangiocarcinoma, 6.89 months (95% CI 5.604–8.505) for patients with non-small cell lung cancer, no death or disease progression at one year follow-up for patients with liver cancer, 11.05 months (95% CI 9.308–12.792) for patients with esophageal cancer, and 9.74 months (95% CI 6.979–12.502) for patients with gastric cancer. It indicates that the clinical benefit was greater in patients with hypothyroidism occurring in patients treated with ICIs in gastric, hepatocellular, and esophageal cancers.

The pathogenesis of ICI-induced thyroid dysfunction encompasses immune-mediated acute inflammation leading to destructive thyroiditis. Although this study utilized small sample size data to confirm that ICI-related thyroid disorders are associated with better disease prognosis, patients still need to be vigilant in the diagnosis and detection of ICI-related thyroid disorders during their treatment, as well as regular thyroid function screening, utilizing measurements of TSH, fT4, TRAb, TPO-antibodies and TSH receptor antibodies, according to specific guidelines [26,27,28]. Therefore, this study has some drawbacks, mainly because the number of cases is too small and there may be large individual differences leading to bias in the data. In addition, the follow-up time was not sufficient to demonstrate long-term survival outcomes. Further studies with larger cohorts are needed to confirm the association between hypothyroidism and the efficacy of ICIs. Based on the results of this study, we can develop a risk score of thyroid dysfunction for patients receiving ICIs treatment, the score for predicting tumour prognosis development could be established. Naturally, such a prediction model should be developed and subsequently validated in separate patient cohorts with sufficient power.

Furthermore, an emerging area of research interest in the field of oncology is whether these two aspects of ICIs can be uncoupled to maximize benefit while minimizing toxicities for patients. IRAEs appear to represent a clinical biomarker for ICI response, albeit one that emerges on treatment. Many questions remain about different types of ICI and irAE, the true nature of the relationship between irAEs characteristics such as site, severity, timing of onset and management and ICI efficacy, the. Prospective well-powered studies need to be performed to understand the true implications of IRAE characteristics on ICI response in patients. In addition, if irAEs can be used as markers for ICIs therapy, then our oncology treatment guidelines need to be updated to make adjustments to the management of prognostic adverse effects of ICIs therapy.