Pembrolizumab for anaplastic thyroid cancer: a case study

Aghajani, Marra Jai; Cooper, Adam; McGuire, Helen M.; Jeffries, Thomas C.; Saab, Jawad; Koçyiğit, İsmail; Souza, Paul de; Bray, Victoria; Groth, Barbara Fazekas de St; Niles, Navin; Roberts, Tara L.

doi:10.1007/s00262-019-02416-7

Cited by 17 publications

(9 citation statements)

References 77 publications

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“…Indeed, PDL1 immunoreactivity is evident in a subset of ATCs, often displaying strong and widespread expression in approximately 80% of tumor cells-mirroring the findings in our case [18,19]. The prognostic significance of this expression pattern is, however, not known, and ATC-related studies with PDL1 inhibitors in the clinical setting are scarce [20,21], although studies with animal models seem promising [22,23].…”

Section: Discussionsupporting

confidence: 77%

Metastatic Anaplastic Thyroid Carcinoma in Complete Remission: Morphological, Molecular, and Clinical Work-Up of a Rare Case

et al. 2020

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Anaplastic thyroid carcinoma (ATC) exhibits an exceedingly poor prognosis, and the current treatment options are, for most cases, palliative by nature. Few reports of long-time survivors exist, although in these patients, tumors often were limited to the thyroid and/or regional lymph nodes. We describe a 64-year-old male who developed a rapidly growing mass in the left thyroid lobe. A fine-needle aspiration biopsy (FNAB) was consistent with ATC, and the patient underwent preoperative combined chemo-and radiotherapy followed by a hemithyroidectomy. The ensuing histopathological investigation was consistent with ATC adjoined by an oxyphilic well-differentiated lesion, likely a Hürthle cell carcinoma. Tumor margins were negative, and no extrathyroidal extension was noted. Focused next-generation sequencing analysis of the primary tumor tissue identified a TP53 gene mutation but could not identify any potential druggable targets. Additional Sanger sequencing detected a C228T TERT promoter mutation. The tumor was found to be microsatellite stable and displayed PDL1 expression in 80% of tumor cells. Following a CT scan 1 month postoperatively, metastatic deposits were suspected in the lung as well as in the left adrenal gland, of which FNAB verified the latter. Remarkably, upon radiological follow-up, the disease had gone into apparent complete remission. The patient is alive and well with no signs of residual disease after 12 months of follow-up. We here summarize the clinical, histological, and molecular data of this highly interesting patient case and review the literature for possible common denominators with other patients with disseminated ATC.

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Section: Discussionsupporting

confidence: 77%

Metastatic Anaplastic Thyroid Carcinoma in Complete Remission: Morphological, Molecular, and Clinical Work-Up of a Rare Case

et al. 2020

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“… 34 Likewise, it was observed that CD4 + T CM cells in peripheral blood were expanded in an anaplastic thyroid cancer patient treated with anti-PD-1 therapy. 35 Our KEGG pathway enrichment analysis indicated that IL-17 signaling pathway might be involved in the improved prognosis in OSCC patients with abundant CD4 + T CM cells. Indeed, IL-17, mainly secreted by T helper 17 cells, has been demonstrated to show an elevated expression in OSCC patients and negatively correlated with the OS of head and neck cancer patients.…”

Section: Discussionmentioning

confidence: 80%

Tumor-Infiltrating CD4+ Central Memory T Cells Correlated with Favorable Prognosis in Oral Squamous Cell Carcinoma

Wu¹,

Zhang²,

Xiong³

et al. 2022

JIR

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Objective Oral squamous cell carcinoma (OSCC) is the most frequent oral malignancy with a poor prognosis, in which tumor-infiltrating immune cells may play a critical role. Therefore, our study aims to screen potential immune cells and immune-related genes for predicting OSCC prognosis. Methods A total of 310 OSCC patients with full transcriptional data and clinical characteristics were extracted from the TCGA database. Then, we obtained their abundance of tumor-infiltrating immune cells on TIMER 2.0 and analyzed them using xCell method. Univariate and multivariate Cox regressions were applied successively to identify the immune cells associated with overall survival of OSCC patients. Furthermore, we screened the prognostic genes that related to the identified immune cells and validated their expressions by immunohistochemistry. Results CD4 + central memory T (T CM ) cell was recognized as the sole independent immune cell correlated with OSCC prognosis ( p = 0.0085). A novel nomogram based on CD4 + T CM cell abundance was established for predicting the prognosis of OSCC patients, with calibration plots showing good performance for 1-, 3-, 5-year overall survival. Thirty-four related prognostic genes were screened according to the differential abundance of CD4 + T CM cell infiltration. In immunohistochemistry analysis, DEFB1 showed a significant positive relationship with the density of CD4 + T CM cells ( p = 0.0075). Conclusion CD4 + central memory T cell was proposed as an independent prognostic biomarker for OSCC patients. DEFB1 might positively regulate the abundance of tumor-infiltrating CD4 + T CM cells, thus improving OSCC prognosis. Our findings may provide a new insight into better prognosis prediction and precise medicine for OSCC.

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“…The study and development of alternative therapeutic strategies is essential in order to improve the quality of life and prognosis of affected patients. Immunotherapeutic agents, including pembrolizumab [15], atezolizumab [16], tyrosine kinase inhibitors such as levatinib [17,18] and oncolytic virus therapy [19,20] are currently under investigation and have demonstrated promising results in preliminary trials.…”

Section: Discussionmentioning

confidence: 99%