American Association for Cancer Research
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Figure S5 from Lenalidomide Augments the Antitumor Activities of Eps8 Peptide-Specific Cytotoxic T Lymphocytes against Multiple Myeloma

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posted on 2023-04-03, 15:30 authored by Xiaoling Xie, Yiran Chen, Yuxing Hu, Yanjie He, Honghao Zhang, Yuhua Li

Representative flow cytometric analysis images (A) and relative quantification (B) of PD-1+ expression on CD3+CD8+ T cells. These data demonstrated that the Eps8cocktail@len treatment downregulated PD-1 expression on CD3+CD8+ T cells in the tumors. All data represent the mean {plus minus} SD (n = 3). *P < 0.05 and **P < 0.01.

Funding

Science and Technology Program of Guangzhou, China

Natural Science Foundation of Guangdong Province, China

Guangzhou Regenerative Medicine and Health Guangdong Laboratory, China

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ARTICLE ABSTRACT

Cancer immunotherapy is a promising new approach to cancer treatment. It has been demonstrated that a high number of tumor-specific cytotoxic T cells (CTL) is associated with increased survival in patients with multiple myeloma. Here, we focused on EGFR pathway substrate 8 (Eps8) as a candidate tumor-associated antigen (TAA) in multiple myeloma. Previous work has shown that Eps8-based immunotherapy in HLA-A2+ cancer patients may result in efficient antitumor immune responses against diverse tumor types. To improve immunotherapy for patients with multiple myeloma, we constructed a cocktail vaccine by combining several HLA-A2–restricted epitopes derived from Eps8 (Eps8cocktail), including Eps8101-2L (WLQDMILQV), Eps8276-1Y9V (YLDDIEFFV), and Eps8455-1Y (YLAESVANV). The CTLs induced by Eps8cocktail (Eps8cocktail-CTLs) showed highly effective anti–multiple myeloma activity, including Th1 cytokines production, cell proliferation, and cytotoxicity against HLA-A2+ multiple myeloma cells. This study highlights the importance of using a cocktail vaccine instead of a single-peptide vaccine to induce a robust response. Importantly, we revealed that lenalidomide effectively stimulated the antitumor activity of the Eps8cocktail-CTLs, with increasing expression trends for T-cell markers (CD28, CD40L, 41BB, and OX40). Compared with unstimulated CTLs and Eps8cocktail-CTLs, lenalidomide-treated Eps8cocktail-CTLs showed superior anti–multiple myeloma activity in humanized multiple myeloma models, including delaying tumor burden increases due to enhanced immune function. These results provide the framework for an Eps8 cocktail vaccination therapy to induce effective Eps8-specific CTLs in HLA-A2+ patients with multiple myeloma. Moreover, these studies further demonstrate that lenalidomide augments the immune response, providing a possibility for its use in combination with peptide vaccines to improve patient outcomes.

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