Harnessing the latest proteomics approaches in the fight against skin cancer

Sunshine in moderation is good for you, but too much exposure without adequate protection can lead to melanoma – the most dangerous type of skin cancer due to its ability to spread to other organs rapidly if not treated early. Treatment has come a long way since the first immunotherapy for melanoma, which was an immune checkpoint inhibitor launched in 2011, but some tumors continue to show resistance and understanding the biology of tumor progression or remission is a complex field.

Rising to that challenge is Dr. Genevieve Boland, a surgical oncologist at the Massachusetts General Hospital in Boston, USA, who directs the Melanoma/Sarcoma Surgery Program and is also an Assistant Professor at the Harvard Medical School. Driven by patient need, Dr. Boland explores melanoma progression to try to understand why current standard-of-care therapies do or do not work. Dr. Boland is supported in this endeavor by cutting-edge proteomics approaches and other technologies, ultimately seeking to identify better therapies, better ways of stratifying risk, and improving outcomes for melanoma patients.

Tracking biomarkers in tumors and plasma

Dr. Boland is interested in the basic biology behind melanoma progression, from initial primary tumors to metastases, as well as questions relating to therapy response and resistance. This requires a suite of technologies aimed at both the level of the solid tumor and at biomarkers circulating in the blood, with proteomics taking center stage: “Proteomics is such an important part of the readout of what’s changing at both the level of the tumor and within the immune system,” explains Boland.

There are many techniques that can be implemented to analyze tumors, “when we analyze the tumor, we use multiplex immunofluorescence which really helps us understand protein expression and cytopathology. But in the blood, things become a little more challenging, and most recently we have been using Olink Proteomics’ proximity extension assay,” Boland says.

When it comes to the choice of technology, it is very much horses for courses. Context is crucial, as Boland attests: “There’s a variety of approaches, but it really depends upon how focused your question is – do you know exactly what you’re looking for to query the tumor or the blood, or is your question more broad requiring you to look more widely?”

It seems that a multi-layered approach can be beneficial, with several technologies complementing one another, but do some have more traction than others?

Plasma proteomics: Horses for courses

Boland indicates that there has been a history of looking at circulating immune cells, such as PBMCs and T cell populations, or even circulating tumor cells to track cancer, although tumor benchmarking may be less helpful in predicting or monitoring immunotherapy response. “In immuno-oncology, one has to think about both the tumor and how changes in the tumor microenvironment or immune cell populations are occurring concurrently,” she says. “We have a project with Olink looking at a large panel of circulating proteins in the setting of immunotherapy response and resistance, and I think that this really has traction,” Boland adds.

According to Boland, the ability of plasma proteomics to read out both intrinsic changes to tumors and changes arising from the immune system is a clear benefit over other approaches, such as circulating tumor DNA: “We’ve been able to overlay plasma proteomics with single-cell RNA sequencing of tumor-infiltrating lymphocytes, to see if not only can we define what changes in the plasma proteome are occurring with response and resistance over time, but also deconvolute or map these changes back to specific immune cell populations within the tumor,” she enthuses.

Further technology benefits

Boland elaborates on the benefits she has found in using Olink Proteomics’ technology: “One of the benefits of Olink over other platforms that we’ve tried in the past is its reproducibility,” she says. “Other benefits are the breadth of the proteins that one can look at and the small sample input.”

This latter benefit is a “huge advantage” according to Boland, who speaks reverently of the gracious donation of samples by patients, with which she can only do so much. If a single analysis uses up an entire sample, this undermines her ability to build large, linear datasets over time.

Future impacts

Boland concludes with a summary of her aspirations for her research: “I really do hope it will improve patient care,” she says. “I really think that what we’re learning from studying both the tumors and these blood-based biomarkers will hopefully feed back and inform risk stratification, even patient selection for therapy, and assist in monitoring patients over time.”

Ultimately, it is all about understanding and treating patients better in the future.

Find out more about the work of the Boland lab and how Olink Proteomics’ Explore 1536 NGS proteomic platform could help you>>