Evidence of Antitumor and Antimetastatic Potential of Induced Pluripotent Stem Cell-Based Vaccines in Cancer Immunotherapy

Abstract

Cancer is maintained by the activity of a rare population of self-renewing “cancer stem cells” (CSCs), which are resistant to conventional therapies. CSCs over-express several proteins shared with induced pluripotent stem cells (iPSCs). We show here that allogenic or autologous murine iPSCs, combined with a histone deacetylase inhibitor (HDACi), are able to elicit major anti-tumor responses in a highly aggressive triple-negative breast cancer, as a relevant cancer stemness model. This immunotherapy strategy was effective in preventing tumor establishment and efficiently targeted CSCs by inducing extensive modifications of the tumor microenvironment. The anti-tumoral effect was correlated with the generation of CD4+, CD8+ T cells, and CD44+ CD62L- CCR7low CD127low T-effector memory cells, and the reduction of CD4+ CD25+FoxP3+ Tregs, Arg1+ CD11b+ Gr1+, and Arg1+ and CD11b+ Ly6+ myeloid-derived suppressor cell populations within the tumor. The anti-tumoral effect was associated with a reduction in metastatic dissemination and an improvement in the survival rate. These results demonstrate for the first time the clinical relevance of using an off-the-shelf allogeneic iPSC-based vaccine combined with an HDACi as a novel pan-cancer anti-cancer immunotherapy strategy against aggressive tumors harboring stemness features with high metastatic potential.

Comprehensive analysis of the potential cuproptosis-related biomarker LIAS that regulates prognosis and immunotherapy of pan-cancers

“…Innate immune cells could trigger the adaptive immune responses, and understanding of cancer-intrinsic processes will supply the exploration and development of immunotherapy ( 26 , 27 ). Cancer-associated fibroblast was reported to induce cancer cell proliferation, invasion, and metastasis through various pathways ( 28 , 29 ).…”

“…Cancer-associated fibroblast was reported to induce cancer cell proliferation, invasion, and metastasis through various pathways ( 28 , 29 ). Moreover, Tregs that expressed the transcription factor Foxp3 could possess importance in immune homeostasis ( 26 , 30 ). In this study, we found that LIAS expression was strongly correlated with the infiltration of immune cells, including B cell, cancer-associated fibroblast, T cell CD8+, DC, macrophage, and Tregs.…”

Comprehensive analysis of the effects of the cuprotosis-associated gene SLC31A1 on patient prognosis and tumor microenvironment in human cancer

“…Adaptive immune responses may be triggered by innate immune cells, and research into and the development of immunotherapy will be aided by knowledge of the internal workings of cancer ( 32 , 33 ). According to Schalper et al and Bremnes et al ( 34 , 35 ), type I immune responses are typically associated with CD8 + T cells and T cells triggered by CD4 + type 1 T helper cells, and they are associated with a positive prognosis for lung cancer patients.…”

Pan-cancer analysis of the cuproptosis-related gene DBT that serves as an immunotherapy and prognostic biomarker

“…It has been con rmed that the occurrence, development and treatment of tumors are relevant to tumor immune cell in ltration (20,21). In our study, we found that the expression of DBT was signi cantly positively related with immune in ltration level in diverse cancer types, included T cell CD8+ in PAAD and UM, neutrophil in BRCA, PRAD and KIRC, cancer associated broblast in HNSC, PAAD, STAD and THYM, endothelial cell in COAD, HNSC, KIRC and LUAD.…”