Left: Field emission scanning electron microscopy (FESEM) image shows the development of a nanotube in between a breast cancer cell and an immune cell.: Confocal microscopy image reveals mitochondria (labeled with green fluorescence dye) taking a trip from a T cell to a cancer cell through the intercellular nanotube. Slurping out the immune cells mitochondria powers up the cancer cell and diminishes the immune cell. To examine how cancer cells and immune cells connect at the nanoscale level, Sengupta and coworkers set up experiments in which they co-cultured breast cancer cells and immune cells, such as T cells. The team then stained mitochondria– which provide energy for cells– from the T cells with a fluorescent color and watched as brilliant green mitochondria were pulled out of the immune cells, through the nanotubes, and into the cancer cells.
To examine how cancer cells and immune cells engage at the nanoscale level, Sengupta and coworkers set up experiments in which they co-cultured breast cancer cells and immune cells, such as T cells. Using field-emission scanning electron microscopy, they caught a peek of something uncommon: Cancer cells and immune cells seemed physically connected by small tendrils, with widths primarily in the 100-1000 nanometer variety. (For comparison, a human hair is roughly 80,000 to 100,000 nanometers). In some cases, the nanotubes came together to form thicker tubes. The team then stained mitochondria– which offer energy for cells– from the T cells with a fluorescent color and watched as intense green mitochondria were pulled out of the immune cells, through the nanotubes, and into the cancer cells.
” By thoroughly maintaining the cell culture condition and observing intracellular structures, we saw these fragile nanotubes and they were taking the immune cells energy source,” said co-corresponding author Hae Lin Jang, PhD, a primary private investigator in the Center for Engineered Therapeutics. “It was extremely exciting because this sort of habits had never been observed prior to in cancer cells. This was a difficult project as the nanotubes are delicate and we had to deal with the cells very carefully to not break them.”.
The researchers then aimed to see what would occur if they avoided the cancer cells from hijacking mitochondria. They saw a considerable decrease in tumor development when they injected an inhibitor of nanotube formation into mouse models used for studying lung cancer and breast cancer.
” One of the goals in cancer immunotherapy is to discover mixes of treatments that can improve results,” said lead author Tanmoy Saha, PhD, a postdoctoral researcher in the Center for Engineered Therapeutics. “Based on our observations, there is evidence that an inhibitor of nanotube development could be integrated with cancer immunotherapies and evaluated to see if it can enhance results for clients.”.
Referral: “Intercellular nanotubes moderate mitochondrial trafficking in between cancer and immune cells” by Tanmoy Saha, Chinmayee Dash, Ruparoshni Jayabalan, Sachin Khiste, Arpita Kulkarni, Kiran Kurmi, Jayanta Mondal, Pradip K. Majumder, Aditya Bardia, Hae Lin Jang and Shiladitya Sengupta, 18 November 2021, Nature Nanotechnology.DOI: 10.1038/ s41565-021-01000-4.
Disclosures: Sengupta is a co-founder and owns equity in Vyome Therapeutics, Akamara Therapeutics and Invictus Oncology, and gets costs from Famygen and Advamedica. Jang owns and is a creator equity in Curer. A full list of other author disclosures is readily available online.
Financing: This work is supported by grants from the National Institute of Health (NIH AR073135_HLJ, CA236702_SS_HLJ, CA214411_SS and CA229772_SS_Co-I), American Lung Association Discovery Grant (LCD-618834_SS) and Department of Defense (DoD PC180355_HLJ and CA201065_HLJ). This work was performed in part at the Center for Nanoscale Systems (CNS), Harvard University, a member of the National Nanotechnology Coordinated Infrastructure Network (NNCI), supported by the National Science Foundation.
Left: Field emission scanning electron microscopy (FESEM) image reveals the development of a nanotube in between a breast cancer cell and an immune cell.: Confocal microscopy image shows mitochondria (labeled with green fluorescence dye) taking a trip from a T cell to a cancer cell through the intercellular nanotube.
With the power of nanotechnology, investigators have found that cancer cells strengthen by forming nanotubes that they utilize to suck mitochondria out of immune cells.
To grow and spread out, cancer cells need to evade the immune system. Detectives from Brigham and Womens Hospital and MIT used the power of nanotechnology to find a new manner in which cancer can deactivate its prospective cellular enemies by extending out nanoscale tentacles that can reach into an immune cell and pull out its powerpack. Slurping out the immune cells mitochondria powers up the cancer cell and diminishes the immune cell. The brand-new findings, released in Nature Nanotechnology, could result in new targets for developing the next generation of immunotherapy against cancer.
” Cancer eliminates when the immune system is suppressed and cancer cells are able to metastasize, and it appears that nanotubes can assist them do both,” said matching author Shiladitya Sengupta, PhD, co-director of the Brighams Center for Engineered Therapeutics. “This is a completely brand-new mechanism by which cancer cells evade the immune system and it provides us a new target to go after.”.
