Sunday, April 17, 2022

Melanoma: Getting Under Our Skin

Good news! Very impressive research! Cancer is history (soon)!

"Fortunately, when caught early, melanoma can often be cured by simple surgery, and there are now better treatments for advanced cases, including immunotherapies that prime a patient’s immune system to fight off the cancer.
However, much remains unknown about melanoma, including the details of how it develops in the earliest stages, and how to best identify and treat the most dangerous early cases. ...
Now, a team at Harvard Medical School has created spatial maps at the single-cell level that reveal, in unprecedented detail, how melanoma cells and nearby cells, including immune cells, interact as a tumor develops. ...
The HMS team is building the maps into a melanoma atlas that will be freely available to the scientific community as part of the National Cancer Institute’s Human Tumor Atlas Network. They hope that eventually, the atlas can serve as a jumping-off point for scientists to study how to prevent melanoma and how to treat it in its nascent stages before it becomes full-blown cancer. ...
Such spatial resolution, along with fine-scale molecular data, became possible to achieve only recently with the advent of more advanced single-cell imaging technologies, including cyclic immunofluorescence, or CyCIF, a multiplexed imaging technique developed by the Sorger lab.
In the new paper, the researchers combined CyCIF imaging data with 3D high-resolution microscopy and fine-scale RNA sequencing to create maps capturing where cells are located and how they interact as normal tissue morphs into melanoma. ...
With the paper, the researchers are releasing the largest imaging-based melanoma dataset to date—and the entire dataset will be freely available through Minerva, an online visualization tool the lab developed to make complex data easier to understand and use. ...
The researchers are building the maps into an open-source melanoma atlas within the Human Tumor Atlas Network that captures the full range of molecular interactions between cells in different stages of disease. They envision the atlas having a similar impact as earlier atlases of cancer genomics, including The Cancer Genome Atlas. Ultimately, they hope that their work will propel novel insights in melanoma that lead to precision-targeted individualized treatments based on a patient’s tumor characteristics. ..."

From the abstract:
"... Here we integrate high-plex imaging, 3D high-resolution microscopy, and spatially-resolved micro-region transcriptomics to study immune evasion and immunoediting in primary melanoma. We find that recurrent cellular neighborhoods involving tumor, immune, and stromal cells change significantly along a progression axis involving precursor states, melanoma in situ, and invasive tumor. Hallmarks of immunosuppression are already detectable in precursor regions. When tumors become locally invasive, a consolidated and spatially restricted suppressive environment forms along the tumor-stromal boundary. This environment is established by cytokine gradients that promote expression of MHC-II and IDO1, and by PD1-PDL1 mediated cell contacts involving macrophages, dendritic cells, and T cells. A few millimeters away, cytotoxic T cells synapse with melanoma cells in fields of tumor regression. Thus, invasion and immunoediting can co-exist within a few millimeters of each other in a single specimen. ...
Specifically, the maps showed that in the earliest stages of melanoma, so-called precursor lesions were composed of similar types and proportions of cells as normal skin, but these cells had a drastically different pattern of interaction, which included signs of immunosuppression. ...
With the paper, the researchers are releasing the largest imaging-based melanoma dataset to date—and the entire dataset will be freely available through Minerva, an online visualization tool the lab developed to make complex data easier to understand and use. ..."

Getting Under Our Skin | Harvard Medical School Spatial maps of melanoma reveal how individual cells interact as cancer progresses

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