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Aberrant intercellular communication underlies disease progression. For example, cancer cells communicate with neighboring cells using extracellular proteins and physical nanotube formation to gain survival advantages. I investigate such cellular communication mechanistically and design novel therapeutic strategies. Immunotherapy has made a paradigm shift in cancer treatment, but it only responds to less than 30% of cancer patients. I have shown how cancer cells use multiple checkpoints to block the immune cells. I have introduced bifunctional immunoengineered nanotherapeutics that can block multiple cancer immune interactions and can deliver pharmacological drugs specifically to the cancer cells. We have shown increased therapeutic efficacy in lung cancer where traditional immunotherapy fails.
Furthermore, we investigated a novel mechanism of immune evasion by cancer cells through nanoscale physical communication. We have used high-resolution electron and optical microscopy to identify the nanotube-mediated mitochondrial hijack by cancer cells from T cells. The transfer of mitochondria metabolically empowers the cancer cells and increases their proliferation, metastasis, and drug resistance. In contrast, the T cell population depletes because of metabolic deactivation. Blocking the nanotube-mediated mitochondria transfer by pharmacological inhibitors has shown potential therapeutic implications in increasing the intrinsic T cell immune response and elevating therapeutic efficacy in combination with traditional immunotherapy.
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