Zhen Han, assistant research professor at City of Hope, and Christiane Querfeld, MD, Ph.D., director of the Cutaneous Lymphoma Program at City of Hope speaks about AACR 2021 – Abstract: 2759 – Reprogramming of PD1+ M2-like tumor-associated macrophages with anti-PD-L1 and Lenalidomide in cutaneous T cell lymphoma.
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Link to Abstract:
https://www.abstractsonline.com/pp8/#!/9325/presentation/4036
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Synopsis:
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TAMs, or M2-like tumor-associated macrophages, are abundant and affect the progression of cutaneous T cell lymphoma (CTCL) by causing immunosuppression. While it is well-founded that M2-like TAMs depletion inhibits CTCL growth, little is known about the underlying mechanisms that form the PD1+ M2-like TAMs phenotype in CTCL. In this study, we discovered that PD1+ M2-like TAMs accumulated in CTCL lesional skin. TLR/NF-B and JAK/STAT signaling pathways were also upregulated in human CTCL tissues, according to RNA-seq review. In vitro, PD1+ TAMs had an M2-like profile, with a substantial increase in CD163, CD206, and IL-10 expression and a strong decrease in CD80, IL-1, CXCL-10, and CXCL-11 expression, as well as activation of the TLR/NF-B and JAK/STAT signaling pathways. Anti-PD-L1 (durvalumab) and lenalidomide were used to treat MyLa-conditioned media mediated human peripheral blood monocyte-derived PD1+ M2-like TAMs in order to see whether they could be reprogrammed. The findings indicate that anti-PD-L1 and lenalidomide worked together in vitro to reshape M2-like TAMs into M1-like TAMs by blocking the TLR/NF-B and JAK/STAT signaling pathways, which was related to functional improvements in phagocytic behavior and cell migration. To summarize, TLR/NF-B and JAK/STAT signaling pathways may push PD1+ M2-like TAM programming in the CTCL tumor microenvironment, while anti-PD-L1 and lenalidomide may reshape PD1+ M2-like TAMs and induce functional changes in CTCL by blocking these pathways.