TP53 mis-sense mutations and one non-sense mutation were detected in three of 15 examined MCCs, suggesting that TP53 mutations may play a role in the pathogenesis or progression of a subset of MCCs.
We describe a case of a 73-year-old man with Merkel cell carcinoma who received the anti-PD-L1 monoclonal antibody avelumab and achieved partial response.
In this study, we obtained MCCs from 21 elderly patients (19 women, 2 men) and analyzed their DNA for mutation of exons of interest in several tumor-suppressor genes or oncogenes known to be frequently mutated in skin cancer: p53 (exons 4-8), Ras (exons 1 and 2), c-Kit (exon 11), and the INK4a-ARF locus (encoding p14 and p16) (exons 1 and 2).
Hence, we analyzed 15 CK20-negative Merkel cell carcinoma tumors (10 Merkel cell polyomavirus-negative, four Merkel cell polyomavirus-positive, and one undetermined) using the Ion Ampliseq Comprehensive Cancer Panel, which assesses copy number alterations and mutations in 409 cancer-relevant genes.
Next generation sequencing of Cytokeratin 20-negative Merkel cell carcinoma reveals ultraviolet-signature mutations and recurrent TP53 and RB1 inactivation.
Interruption of immune checkpoints, such as CTLA-4 and PD-1, has been verified to be a successful means for cancer therapy in clinical trials. mAb targeting PD-L1 has been approved to treat urothelial carcinoma, non-small cell lung cancer, or Merkel cell carcinoma by the FDA.
As anti-CD200 antibody effectively targets CD200 on MCC tumor cells <i>in vivo</i>, this treatment may provide a novel immunotherapy for MCC independent of PD-1/PD-L1 blockade.
The cells around some MCC and non-MCC tumors were stained with CM2B4 with a distribution similar to CD20- and CD45RO- (especially CD8-) positive lymphocytes.
Here, we have performed a comparative study of full-length or MCC-derived truncated LT-Ags with regard to their biochemical characteristics, their ability to bind to retinoblastoma (Rb) and p53 proteins, and their transforming potential.
Avelumab, a human Ig-G1 monoclonal antibody targeting PD-L1 and approved in the USA for the treatment of metastatic Merkel cell carcinoma, has shown antitumour activity and an acceptable safety profile in patients with advanced solid tumours in a dose-escalation phase 1a trial.
While the binomial presence or absence of PD-L1 expression in the TME was not sufficient to predict response to anti-PD-1 in patients with MCC, we show that quantitative assessments of PD-1+ and PD-L1+ cell densities as well as the geographic interactions between these two cell populations correlate with clinical response.
Basal cell carcinoma (BCC) can resemble Merkel cell carcinoma (MCC) on histopathological examination and while CK20 is a useful marker in this differential, it is occasionally negative in MCC.
In this study, we obtained MCCs from 21 elderly patients (19 women, 2 men) and analyzed their DNA for mutation of exons of interest in several tumor-suppressor genes or oncogenes known to be frequently mutated in skin cancer: p53 (exons 4-8), Ras (exons 1 and 2), c-Kit (exon 11), and the INK4a-ARF locus (encoding p14 and p16) (exons 1 and 2).
<b>Conclusion:</b> These data provide important insight on the role of MCPy DNA viral load and TILs in the context of PD-L1 in patients with Merkel cell carcinoma.
Patients with adequate tissue (n = 4), positive neuroendocrine differentiation (chromogranin, synaptophysin, and cytokeratin 20), and histopathological confirmation of MCC were included in the study.
Both virus-positive and virus-negative MCCs are immunogenic, and inhibition of the programmed cell death protein 1 (PD-1)-programmed cell death 1 ligand 1 (PD-L1) immune checkpoint has proved to be highly effective in treating patients with metastatic MCC; however, not all patients have a durable response to immunotherapy.
Avelumab, an anti-PDL1 antibody, was the first drug to be approved internationally as second-line monotherapy for patients with advanced MCC, based on results from the JAVELIN Merkel 200 clinical trial.
Combined MCC differed from conventional MCC in earlier AJCC stage, increased risk of recurrence and death, decreased CD8 infiltrates, more frequent TTF1 positivity (5/8), abnormal p53 expression (8/8), and frequent lack of large T antigen expression (7/8).
More recently, three anti-PD-L1 antibodies have received approval: atezolizumab and durvalumab for locally advanced or metastatic urothelial carcinoma and metastatic non-small cell lung cancer (NSCLC) and avelumab for the treatment of locally advanced or metastatic urothelial carcinoma and metastatic Merkel cell carcinoma.