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Scientist Spotlight: Monica Olcina, D.Phil.

February 05, 2019

The Cancer Research Institute is pleased to showcase the work of CRI grantees and how their research sheds light on the role the immune system plays in our bodies and in the fight against cancer.

Dr. Monica OlcinaBorn in Spain, Monica M. Olcina completed her college studies in England, where she earned her M.Pharm degree at The University of Manchester and then both her M.Sc. and D.Phil. in Radiation Biology at Oxford University. Following her doctorate, she moved to the United States, where she is currently funded by the Cancer Research Institute (CRI) as a postdoctoral fellow in the lab of Amato J. Giaccia, Ph.D., at the Stanford University School of Medicine.

Earlier this month, CRI spoke with Dr. Olcina about her career and the recent progress she’s made in her postdoctoral research studies.


How did you first become interested in the field of cancer immunology and immunotherapy, and what attracted you to the Cancer Research Institute?

My background is not in immunology so I actually did not first come across cancer immunology through my research but instead when I was reading a magazine article about the early work of Dr. James Allison [the director of the CRI Scientific Advisory Council] while on a plane (probably going back to Spain to visit my family over the holidays).

With respect to the Cancer Research Institute, I was very drawn to their background and goals and thought their postdoctoral fellowships were a generous and great way to build my scientific independence during my postdoctoral training, so I decided to apply for a CRI fellowship.

Speaking of your CRI fellowship, I understand that some of your CRI-funded work was just published in the journal Cell Reports and that it deals with an important immune pathway called “complement.” Can you explain a little bit about the complement system and the role it plays in our bodies?

The complement system was first discovered as group of proteins found in the blood that help antibodies in our bodies kill bacteria. Now we know that the complement system has a broader role and can help provide defense against things considered “non-self” such as bacteria and even sometimes our own “dangerous” cells that have become damaged or diseased. When complement proteins are activated in our bodies they help mount different responses including inflammation and/or lysis (“bursting”) of the dangerous cells, thereby helping to remove them from our bodies. Cancer cells can also be considered dangerous “self” cells and should be removed by our immune system, perhaps with the help of the complement system. In fact, the complement system has been recently described to play an important role in cancer progression, which is something that really intrigued us and was one of the reasons why we decided to carry out this work.

In your recent paper, you and your team made some pretty interesting discoveries about complement and its connection to cancer, including how mutations in the complement genes appear to influence patient survival. Could you tell us more about those discoveries?

We found that cancer cells have mutations in the genes that encode the complement proteins, which contributes to the idea that the complement system might indeed play an important role in cancer. In fact, we found that mutations in certain complement genes are associated with decreased probability of survival in patients with colorectal cancer. While our work mainly focused on colorectal cancer, we found mutations in complement genes in a wide range of other cancers. This was surprising to us at first since these mutations had not been previously described in any detail in cancer. The hope is that we can learn more about what effects these mutations have on how tumors grow and respond to treatments. In the future, these mutations could be used to predict who is likely to do better or worse following the diagnosis of different tumor types or following different types of treatment. We look forward to one day, for example, understanding whether the presence of these mutations in a tumor can predict response to immunotherapy.

Your work also focused on hypoxia, which basically just means an environment that is low in oxygen. As your work discussed, tumors are often hypoxic and have low oxygen levels. How does hypoxia fit in with your other findings regarding complement and cancer, especially colorectal cancer?

We were really interested to find that colorectal cancer patients with certain complement mutations also appear to have the most hypoxic tumors, a finding that could help explain the decreased survival rates seen in these patients. We found that there is an important relationship between hypoxia and the amount of complement proteins in colorectal cancer cells, and that these low oxygen (or hypoxic) regions in tumors can contribute to the aberrant regulation of the complement system in cancer.

Another marker that you found to be important with respect to colorectal cancer was CD55, which can regulate the activity of the complement system. What did your work reveal about CD55’s potential impact in cancer, and did those insights suggest any ways that CD55 might be targeted through treatment in order to improve patient outcomes?

As I mentioned earlier, one consequence of complement activation following the encounter of a cell deemed “dangerous” is to trigger the bursting of that cell in order to help remove it from the body. Cancer cells, although in principle dangerous for our bodies, seem to be pretty good at avoiding this bursting, and one of the ways in which they are able to do this is by having high levels of CD55. We found that lysis or “bursting” is particularly inefficient under hypoxic conditions, due at least in part to the fact that hypoxia contributes to colorectal cancer cells having even higher levels of CD55 than usual. In line with high CD55 levels in cancer cells being good for the cancer (and therefore bad for patient survival), we found that colorectal cancer patients that have the highest levels of CD55 also have the lowest chances of surviving long-term following diagnosis. These findings suggest that CD55 might be worth targeting in the future to improve cancer patient outcomes. However, as you mentioned, CD55 is an important regulator of the activity of the complement system so any attempts at targeting it should take into account the other effects this would have on overall complement activation in our bodies.

Finally, could you just talk a little bit about what the support from the Cancer Research Institute has meant to you? Not only the money that has enabled you to carry out this important work, but also the network of scientists with whom you’ve been able to interact and potentially collaborate in the future.

I think one of the best (and most fun) parts of being a Cancer Research Institute fellow is having the opportunity to attend the International Cancer Immunotherapy Conference (CICON) every year. At this meeting not only do you get to hear the main scientists in the cancer immunotherapy field present their work, but it also provides a great platform for all Cancer Research Institute fellows to meet and catch up. This has been a very enriching experience for me every year and it definitely facilitates collaborations. In fact, I met one of the authors of our recently published article (mentioned above) at one of these meetings. I doubt we would have been able to collaborate and carry out this work if I had not heard him give a really interesting talk at this meeting!

Banner photo by Jason Leung on Unsplash.

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