Predictive relevance of programmed cell death protein 1 and tumor-infiltrating lymphocyte expression in papillary thyroid cancer

Aghajani, Marra Jai; Yang, Tao; McCafferty, Charles; Graham, Susannah; Wu, Xiaojuan; Niles, Navin

doi:10.1016/j.surg.2017.04.033

Cited by 35 publications

(47 citation statements)

References 24 publications

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“…The proportion of immune cells in the TME was further tilted towards tumor-promoting immune cells. Previous mainstream studies have shown that TAMs, DCs, MCs, neutrophils, and Tregs are positively correlated with PTC progression [23,32,33,[36][37][38][41][42][43][44][45][46][47][48][49][50][51][52][53], and B cells, CD8 + T cells, NK cells, and iDCs are negatively correlated with PTC progression [49,50,[54][55][56][57][58][59]. Unlike previous studies, our research found that both the abundance and proportion of tumor-promoting immune cells were positively correlated with PTC progression, while the proportion of antitumor immune cells during the progression of PTC decreased (CIBERSORT), and the abundance increased (ssGSEA) or did not signi cantly change (immune cell marker).…”

Section: Discussionmentioning

confidence: 95%

“…Except for M0 macrophages (proportion) in our prognosis studies, other immune cells did not reach signi cant levels. Previous studies in PTC have generally shown that TAMs and neutrophils are associated with a worse prognosis [31,47,[60][61][62], while CD8 + T cells, and DCs are associated with a better prognosis [55,59,63,64]. In fact, the roles of various immune cells in prognosis are still controversial [55,65], and there are many negative results [34,46,[65][66][67].…”

Section: Discussionmentioning

confidence: 99%

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Immune cell confrontation in the papillary thyroid carcinoma microenvironment

Xie

et al. 2020

Preprint

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Background Papillary thyroid carcinoma (PTC) is classified as an inflammation-driven cancer. A systematic understanding of immune cell infiltration in PTC is essential for subsequent immune research and new diagnostic and therapeutic strategies. Methods Three different algorithms, single-sample gene set enrichment analysis (ssGSEA), immune cell marker and CIBERSORT, were used to evaluate the immune cell infiltration levels (abundance and proportion) in 10 data sets (The Cancer Genome Atlas [TCGA], GSE3467, GSE3678, GSE5364, GSE27155, GSE33630, GSE50901, GSE53157, GSE58545, and GSE60542; a total of 799 PTC and 194 normal thyroid samples). Consensus unsupervised clustering divided PTC patients into low-immunity and high-immunity groups. Weighted gene coexpression network analysis (WGCNA) and gene set enrichment analysis (GSEA) were used to analyze the potential mechanisms that cause differences in the immune response. Results Compared with normal tissues, PTC tissues had a higher overall immune level, and the M2 macrophages, Tregs, monocytes, neutrophils, dendritic cells (DCs), mast cells (MCs), and M0 macrophages had higher abundances and proportions in PTC tissues. Compared with early PTC, advanced PTC had higher immune infiltration, and M2 macrophages, Tregs, monocytes, neutrophils, DCs, MCs, and M0 macrophages had higher abundances and proportions in advanced PTC. Compared to the low-immunity group patients, the high-immunity group patients presented with a more advanced stage, a larger tumor size, greater lymph node metastasis, higher tall-cell PTC, lower follicular PTC proportions, more BRAF mutations and fewer RAS mutations. Epstein-Barr virus (EBV) infection was the most significantly enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway for key module genes. Conclusions In human PTC, M2 macrophages, Tregs, monocytes, neutrophils, DCs, MCs, and M0 macrophages played a tumor-promoting role, while M1 macrophages, CD8 + T cells, B cells, NK cells, and T follicular helper (TFH) cells (including eosinophils, γδ T cells, and Th17 cells, with weak supporting evidence) played an antitumor role. During the occurrence and development of PTC, the overall immune level was increased, and the abundance and proportion of tumor-promoting immune cells were significantly increased, indicating that immune escape had aggravated. Finally, we speculate that EBV may play an important role in changing the immune microenvironment of PTC tumors.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Immune cell confrontation in the papillary thyroid carcinoma microenvironment

Xie

et al. 2020

Preprint

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“…As reported in other publications, we explored the possibility of a link between PD-L1 and BRAF V600E. 45,46,48,[58][59][60][61] Angell et al observed that BRAF V600E mutation was associated with immunosuppressive mechanisms in PTC, including PD-L1 expression. 45 According to published reports, the rate of PD-L1 expression is qualitatively and quantitatively higher in BRAF V600E-mutated thyroid lesions, even up to 53% in 1 study.…”

Section: Cancer Cytopathology March 2020mentioning

confidence: 86%

PD‐L1 and thyroid cytology: A possible diagnostic and prognostic marker

Dell’Aquila

Granitto

Martini

et al. 2019

Cancer Cytopathology

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Background Programmed death‐ligand 1 (PD‐L1) expression is emerging as an important predictive biomarker in anti–PD‐L1 cancer immunotherapy. Its role has been clearly defined in various human cancers and is linked to a poor prognosis and resistance to anticancer therapies. The role of PD‐L1 in thyroid cancers has not been well defined in fine‐needle aspiration cytology (FNAC). The authors examined the performance of PD‐L1 immunostaining in liquid‐based cytology (LBC) to determine whether it could be a biomarker of malignancy or aggressive disease. Methods From January 2018 to March 2019, 236 thyroid lesions, which had been diagnosed by FNAC as indeterminate lesions, suspicious for malignancy (SFM), and malignant, were enrolled. PD‐L1 immunostaining was performed on both LBC and corresponding histology samples. Results The FNAC cohort included 50 benign negative controls, 42 samples of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS), 33 samples of follicular neoplasm/suspicious for follicular neoplasm (FN/SFN), 53 samples that were suspicious for malignancy (SFM), and 58 malignant samples. AUS/FLUS samples included 3 goiters, 32 follicular adenomas (FAs), 1 noninvasive follicular thyroid neoplasm with papillary‐like nuclear features (NIFTP), 5 invasive follicular variants of papillary thyroid carcinoma (I‐FVPTCs), and 1 follicular carcinoma; whereas FN/SFN samples included 24 FAs and 9 malignancies (4 I‐FVPTCs, 1 NIFTP, 3 papillary thyroid carcinomas [PTCs], and 1 oncocytic follicular carcinoma). The 53 SFM samples were diagnosed on histopathology as 2 FAs, 5 NIFTPs, 15 I‐FVPTCs, and 31 PTCs; whereas the 58 malignant specimens included 5 NIFTPs, 5 I‐FVPTCs, and 48 PTCs. Increased plasma membrane and cytoplasmic PD‐L1 expression was found in 79 cases (38.5%), including 61 PTCs (conventional and variants). Negative PD‐L1 expression was found in NIFTPs and FAs. A BRAF V600E mutation was identified in 15% of PD‐L1–positive malignancies. Conclusions The current data suggest that PD‐L1 expression in the thyroid gland might represent a marker of malignancy that correlates with PTC, but not with NIFTP. Thyroid neoplasms with PD‐L1 expression also ae enriched with BRAF V600E mutations, suggesting that they are associated with more aggressive behavior.

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“…Other potential biomarkers predictive of response to checkpoint inhibitors have also been assessed in PTC: the tumor mutation burden is generally lowconsistent with what is observed with other endocrine tumors -although immunogenic mutation might still be present [23]. Finally, the presence of a lymphocytic infiltrate in PTC has shown controversial prognostic associations, with most reports, however, suggesting an anti-tumoral role of the inflammatory milieu [24,25].…”

Section: Discussionmentioning

confidence: 99%

Regression of Papillary Thyroid Cancer during Nivolumab for Renal Cell Cancer

Palermo¹,

Napolitano²,

Maggi³

et al. 2020

Eur Thyroid J

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It is already known that papillary thyroid cancer arising in a background of Hashimoto thyroiditis shows increased programmed cell death-1 (PD-L1).• It is already known that metastases to the thyroid gland are uncommon, but frequently associated with renal cancer, especially when presenting as a fast growing nodule. Novel Insights• Our case strongly supports the evaluation of nivolumab and possibly other forms of immune therapy in the treatment of papillary thyroid carcinoma. • The presence of histiocyte aggregates on the site where the prior nodule had been observed supports the hypothesis of an immune-mediated tumor regression. AbstractImmune checkpoint inhibitors have been recently approved for cancer treatment. Nivolumab is a monoclonal antibody specific for programmed cell death-1 (PD-1) that modulates T-cell response. It was initially used for the treatment of ma-lignant melanoma and then approved in other cancers, such as non-small cell lung cancer and clear cell renal cell carcinoma (ccRCC). So far, the activity of nivolumab in patients with thyroid malignancies has been reported in a single case of anaplastic thyroid cancer. Here, we report the case of a patient with ccRCC who developed a papillary thyroid carci-Andrea Palermo and Andrea Napolitano contributed equally to this work.Palermo et al.noma (PTC) under first-line sunitinib treatment. During nivolumab, the second-line treatment for ccRCC, we unexpectedly observed a complete regression of PTC.

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Predictive relevance of programmed cell death protein 1 and tumor-infiltrating lymphocyte expression in papillary thyroid cancer

Cited by 35 publications

References 24 publications

Immune cell confrontation in the papillary thyroid carcinoma microenvironment

Immune cell confrontation in the papillary thyroid carcinoma microenvironment

PD‐L1 and thyroid cytology: A possible diagnostic and prognostic marker

Regression of Papillary Thyroid Cancer during Nivolumab for Renal Cell Cancer

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