Abstract
Tumor antigen-specific redirection of cytotoxic T cells (CTLs) or natural killer (NK) cells including chimeric antigen receptor (CAR-) and T cell receptor (TCR-) cell therapy is currently being evaluated in different tumor entities including melanoma. Expression of melanoma-specific antigen recognized by the respective CAR or TCR directly or presented by HLA molecules is an indispensable prerequisite for this innovative therapy. In this study, we investigated in 168 FFPE tumor specimens of patients with stage I-IV melanoma the protein expression of HER2, TRP2, ABCB5, gp100, p53, and GD2 by immunohistochemistry (IHC). These results were correlated with clinical parameters. Membrane expression of HER2 and GD2 was also investigated in ten melanoma cell lines by flow cytometry for which corresponding tumors were analyzed by IHC. Our results demonstrated that gp100 was the most frequently overexpressed protein (61%), followed by TRP2 (50%), GD2 (38%), p53 (37%), ABCB5 (17%), and HER2 (3%). TRP2 expression was higher in primary tumors compared to metastases (p = 0.005). Accordingly, TRP2 and ABCB5 expression was significantly associated with lower tumor thickness of the primary (p = 0.013 and p = 0.025). There was no association between protein expression levels and survival in advanced melanoma patients. Flow cytometric analysis revealed abundant surface expression of GD2 and HER2 in all melanoma cell lines. The discordant HER2 expression in situ and in vitro suggests a tissue culture associated induction. In summary, our data support the use of gp100 and GD2 as a potential target for developing engineered TCR- or CAR-cell therapies, respectively, against melanoma.
Highlights
Immunotherapeutic approaches gain continuously increasing importance against cancer
To confirm the immunohistochemically found surface expression of GD2 and to investigate the rare and confined expression of HER2 in melanoma metastases, we investigated their expression in ten patient-derived melanoma cell lines grown from fresh melanoma biopsies from the same lesion using flow cytometry
Tumor antigen-specific redirection of T or natural killer (NK) cells represents a promising therapy against melanoma
Summary
Immunotherapies with immune checkpoint blockers made it possible to even cure patients [1,2]. More specific immunotherapies against the melanoma might be more efficacious. Tumor antigen-specific redirection of cytotoxic T cells (CTLs) including chimeric antigen receptor (CAR-) and T cell receptor (TCR-) T cell therapy showed huge success in hematological malignancies, and its efficacy is currently being evaluated in different solid tumors including melanoma [3,4,5]. Melanoma is a very aggressive form of skin cancer and is known for its immunogenic features [6]. Identification and selection of an ideal melanoma-associated antigen that can be recognized by the CTLs or natural killer (NK) cells remain a challenging step for a successful engineered cell-based therapy in melanoma
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
