Using T‐cell repertoire profiles as predictor in a primary mucosal melanoma

Abstract

Dear Editor, Primary mucosal melanoma is a rare subtype of melanoma that carries poor prognosis. Traditional treatment options of mucosal melanoma are surgery, radiation, and chemotherapy; but the overall survival remains low. 1 Cytotoxic T-lymphocyte associated protein 4 (CLTA-4) and programmed cell death protein 1 (PD-1), both inhibitory immune checkpoints commonly seen on activated T cells, have been found to be promising targets for treatment of advanced cancers. 2 However, the efficacy and response to immunotherapy in mucosal melanoma remains unknown. Herein, we report a case involving a patient, who was a 70-year-old male and referred to Taipei Medical University Hospital with confirmed diagnosis of mucosa melanoma over hard plate of mouth. The patient was admitted and subjected to anti-PD-1 immunotherapy (pembrolizumab 200 mg every 3 weeks) (Figure 1A). Serial imaging of primary malignant melanoma of the hard palate showed that the tumor size gradually decreased after treatment with pembrolizumab, suggesting partial response/stable disease secondary to continuous immunotherapy (Figure 1B). However, after seventh cycle of treatment, magnetic resonance imaging (MRI) revealed enlarged previous known metastatic lesions and new tumor nodules in brain (Figure 1B). The patient received stereotactic radiation therapy before treatment cycle 14 (Figure 1A). Although the primary metastatic brain lesions were smaller and stationary after radiotherapy, the following brain MRI displayed several hyperdensity masses in the right frontal lobe with perifocal edema and mild mass effect (Figure 1B). Subsequently, patient suffered from infection and respiratory distress and died 2 months after 17 th cycle of pembrolizumab therapy. To monitor changes in patient's circulating T-cell repertoire at each cycle of immunotherapy, high-throughput TCRβ sequencing of peripheral blood mononuclear cells (PBMCs), isolated from the patient's peripheral blood, was performed using a rapid amplification of 5′ complemen-This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Profiling of T Cell Repertoire in SARS-CoV-2-Infected COVID-19 Patients Between Mild Disease and Pneumonia

“…RNA was extracted from COVID-19 patients’ peripheral blood mononuclear cells (PBMCs) using a Trizol-based method (Thermo Fisher Scientific, MA, USA). Library preparation of T cell receptor beta chain (TCRβ) repertoire for high-throughput sequencing (HTS) was performed as previously described [ 16 ]. Purified RNA sample was first subjected to template-switching reverse transcription polymerase chain reaction (RT-PCR) using SMARTer PCR cDNA Synthesis Kit (Takara Bio USA, CA, USA) and a modified cDNA synthesis (CDS) oligo (5′-CGG GGT ACG ATG AGA CAC CAT TTT TTT TTT TTT TTT TTT TVN-3′).…”

Divergent Characteristics of T-Cell Receptor Repertoire Between Essential Hypertension and Aldosterone-Producing Adenoma

“…The preparation of TCR libraries for TCR sequencing was performed as previously described ( 29 , 32 ). In brief, cDNA was synthesized from extracted RNA using the Switching Mechanism At 5′ end of RNA Template (SMART) technology with SMARTer PCR cDNA Synthesis Kit (Takara Bio USA, CA, USA) and a self-modified cDNA synthesis (CDS) oligo (5′-CGG GGT ACG ATG AGA CAC CAT TTT TTT TTT TTT TTT TTT TVN-3′).…”

“…The sequencing raw data generated in a FASTQ format were subjected to trimming, filtering, alignment, and assembly processes as previously described ( 29 , 32 ). Firstly, TSO and Illumina adaptor sequences were removed, respectively, from the 5′ and 3′ ends of raw sequencing reads using Cutadapt (version 3.0).…”

“…Therefore, an emerging view is that PA and APA are linked to genetic mutations and immune dysregulation. Changes of the immune repertoire have been reported in the response to virus infection, in the progression of kidney diseases, and in the development of tumors ( 25 – 29 ). However, whether PA and APA patients exhibit divergent profiles of T-lymphocyte repertoire remains elusive.…”