The Sentinel

THE OFFICIAL BLOG OF THE SOCIETY FOR IMMUNOTHERAPY OF CANCER (SITC).

Thursday, January 4, 2018

In to I-O: First Contact

by Dr. Nils Rudqvist

My name is Nils Rudqvist and I have a confession to make: a few years ago, fresh out of grad school, I barely knew what a T cell was. I knew even less about dendritic cells, and don’t get me started on macrophages. I mean, I knew of them, but my understanding was very limited. I understood that the immune system worked hard to keep me safe and healthy, but also that it could malfunction - evident from my friend’s constant joint pain.

During my studies in radiation physics, one of the most fascinating subjects was the abscopal effect. The abscopal effect is defined as the ability of radiation therapy to kill an out-of-field distant tumor, without any other systemic treatment, i.e., magic. We were taught that the abscopal effect was incredibly rare and more or less clinically irrelevant. I remember thinking of the abscopal effect as an almost mythical creature, an uncharted territory of radiation therapy that was otherwise so well mapped out. This was back in 2008, and little did I know that Sandra Demaria and Silvia Formenti had already in 2004 demonstrated that the abscopal effect was immune mediated and required T cells that recognized and killed tumor cells.

It took many years before I encountered the abscopal effect again, but my fascination never faded completely. Eventually, the stars aligned and my path started to more frequently cross those of Sandra and her team. In June 2016, I joined Sandra’s lab at Weill Cornell Medicine, where I now research the ins and outs of the abscopal effect. In particular, I investigate how the TCR repertoire is shaped by radiation therapy and immune checkpoint blockade, and the role of neoantigens in the treatment response.

I have a diverse background with training in math and physics and in medical science and biology. I truly believe that multidisciplinary environments, sometimes through serendipity, foster the discovery of findings that would otherwise remain hidden. This is incredibly important, because it feels to me that we are only in the beginning of the immune-oncology revolution.

With my blog posts, I will try to give somewhat of an “outsider’s” perspective of immuno-oncology, although I assume I will eventually transition to become more of an insider. In my next post, I will tell you more about the abscopal effect, and why I am so excited over using radiation therapy to create a patient-specific in-situ vaccination, instead of using it only for local tumor control.

Till next time,

Nils-Petter Rudqvist

2 comments:

  1. I am glad that you came up with the „Apscopal effect” issue, as it is an exciting and complex issue. Please answer these questions in your next summary: Is there any chance for patients with late stage metastatic cancers to benefit from the apscopal effect? Which are the cancer types, where apscopal effect occures more often? What are those characteristics of the tumor and the tumor microenvironment that could be beneficial for the abscopal effect?
    Thanks: Beatrix Kotlan/ kotlanbea@gmail.com

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  2. Dear Beatrix,

    Thanks for your comment and suggestions. Since I am no clinician, I am probably not the best person to answer your questions. However, I believe the answers to your questions are currently not completely known. My understanding is that finding the answers to these key questions is the focus of several research groups, including the one I am part of at Weill Cornell. If you have the chance, I suggest you sign up for the upcoming conference on radiation therapy and immunotherapy combinations, in Paris, later this year: http://www.radio-immuno.siricsocrate.fr/. This is a great meeting at which these questions will be addressed.

    Best,
    Nils

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