TY - JOUR
T1 - Distinguishing melanophages from tumor in melanoma patients treated with talimogene laherparepvec
AU - Audrey-Bayan, Claire
AU - Trager, Megan H.
AU - Gartrell-Corrado, Robyn D.
AU - Rizk, Emanuelle M.
AU - Pradhan, Jaya
AU - Silverman, Andrew M.
AU - Lopez, Adriana
AU - Marks, Douglas K.
AU - Niedt, George
AU - Geskin, Larisa J.
AU - Saenger, Yvonne M.
N1 - Funding Information:
The authors of this publication were supported by the National Institutes of Health through Grant Numbers R01FD006108 (Y.M.S.) and KL2TR001874 (R.D.G.-C.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Y.S. is also supported by funding from the Melanoma Research Alliance and by an Irving Assistant Professorship at Columbia University's NIH/NCATS CTSA Program hub: UL1TR001873. R.D.G.-C. is also supported by Swim Across America. The funding sources had no role in the preparation of the manuscript or the decision to submit for publication.
Publisher Copyright:
© 2020 Lippincott Williams and Wilkins. All rights reserved.
PY - 2020/8/1
Y1 - 2020/8/1
N2 - Response to talimogene laherparepvec (T-Vec) is difficult to assess as pigmented macrophages that have ingested melanoma cells ('melanophages') persist after injection, mimicking melanoma. We used quantitative immunofluorescence (qIF) to (1) distinguish melanophages from melanoma in biopsies from two patients treated with T-Vec and (2) evaluate the tumor microenvironment pretreatment and posttreatment. Tissues were stained with 4',6-diamidino-2-phenylindole, cluster of differentiation (CD) 3, CD8, CD68, human leukocyte antigen-DR isotype (HLA-DR), and SRY-Box Transcription Factor 10 (SOX10), and multispectral images were analyzed. Post-T-Vec samples showed melanophages with cytoplasmic costaining of CD68, SOX10, and HLA-DR, without nuclear SOX10 expression. qIF revealed a dense immune infiltrate of CD3+, CD8+, and CD68+cells in post-T-Vec samples. Melanophages from tumors post-T-Vec stain the nuclear melanoma marker SOX10 in their cytoplasms as compared to melanoma cells that stain nuclear SOX10. This novel finding highlights the phagocytosis of melanoma cell components by macrophages after treatment with T-Vec. qIF may assist pathologists in determining whether lesions treated with immunotherapy contain residual viable melanoma.
AB - Response to talimogene laherparepvec (T-Vec) is difficult to assess as pigmented macrophages that have ingested melanoma cells ('melanophages') persist after injection, mimicking melanoma. We used quantitative immunofluorescence (qIF) to (1) distinguish melanophages from melanoma in biopsies from two patients treated with T-Vec and (2) evaluate the tumor microenvironment pretreatment and posttreatment. Tissues were stained with 4',6-diamidino-2-phenylindole, cluster of differentiation (CD) 3, CD8, CD68, human leukocyte antigen-DR isotype (HLA-DR), and SRY-Box Transcription Factor 10 (SOX10), and multispectral images were analyzed. Post-T-Vec samples showed melanophages with cytoplasmic costaining of CD68, SOX10, and HLA-DR, without nuclear SOX10 expression. qIF revealed a dense immune infiltrate of CD3+, CD8+, and CD68+cells in post-T-Vec samples. Melanophages from tumors post-T-Vec stain the nuclear melanoma marker SOX10 in their cytoplasms as compared to melanoma cells that stain nuclear SOX10. This novel finding highlights the phagocytosis of melanoma cell components by macrophages after treatment with T-Vec. qIF may assist pathologists in determining whether lesions treated with immunotherapy contain residual viable melanoma.
KW - immunotherapy
KW - melanoma
KW - oncolytic virus
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U2 - 10.1097/CMR.0000000000000661
DO - 10.1097/CMR.0000000000000661
M3 - Article
C2 - 32379409
AN - SCOPUS:85087531318
SN - 0960-8931
VL - 30
SP - 410
EP - 415
JO - Melanoma Research
JF - Melanoma Research
IS - 4
ER -