We compared the tumor microenvironment of PD-L1 and PD-L1 areas in a case series of MCC searching for foci evocative of PD-1/PD-L1 adaptive immune resistance.
For this reason, we proposed a novel eye-based "immunoscore" model, obtained by tumor infiltrating lymphocytes subtyping (CD3, CD8, FoxP3, and PD-L1) that could provide additional prognostic information in Merkel cell carcinoma.
In conclusion, there are increasing reports of TTF1+ CK20- skin lesions without signs of systemic disease which behave clinically and prognostically like a PCNC.
Our findings suggest that HDACi may be useful to overcome HLA class-I downregulation as a resistance mechanism against anti-PD-1/PD-L1 antibodies in MCC patients.
Avelumab is a human IgG1 antibody directed against PD-L1 approved for Merkel cell carcinoma and urothelial carcinoma that could be useful also for the treatment of GC.
PD-1/PD-L1 inhibitors are considered the standard of care in advanced MCC and are currently being investigated in the adjuvant and neoadjuvant settings.
<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.
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.
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.
Moreover, 8/9 (89%) CK20-negative Merkel cell carcinoma cases but only 3/61 (5%) CK20-negative extracutaneous neuroendocrine cases were positive for at least one of these markers.
Herein, we present a case of durable response of metastatic Merkel cell carcinoma treated with concurrent radiation and pembrolizumab, providing evidence that radiation might improve systemic responses to anti-PD1/PD-L1 directed immune therapy.
Examination of three cases of combined MCC led to the unexpected discovery that numerous keratin 20 (CK20)-positive MCs within the squamous cell carcinoma (SCC) component of combined MCC appeared morphologically normal with dendritic and oval shapes.
Further, mPDCD1<sub>high</sub> was strongly associated with older age (81 vs 76 years, p = 0.042), absence of immune cells (92.6%, p < 0.001), no expression of PD-L1 by immune cells (70.4%, p = 0.041) and by both immune and tumor cells (70.4%, p = 0.001). mPDCD1 is a valid prognostic parameter in patients affected by Merkel cell carcinoma.
Avelumab is an anti-programmed cell death ligand 1 (PD-L1) antibody approved for treatment of Merkel cell carcinoma (MCC) and locally advanced or metastatic urothelial carcinoma.
Although CK20was negative, the NEC exhibited an immunophenotype suggestive of a Merkel cell carcinoma with diffuse positive staining with FLI-1, SATB2 and neurofilament, markers which are preferentially expressed in Merkel cell carcinoma compared with other NECs.