AIRRC5 - Inferring the impact of proton vs photon radiotherapy with TCR sequencing (J. Heather)
93 بار بازدید -
4 سال پیش
-
Session from the "AIRR Community
Session from the "AIRR Community Meeting V – Zooming in to the AIRR Community!" (December 8-10, 2020)
The meeting covers progress reports from the AIRR-C Working Groups & Sub-committees, two scientific sessions (including four short talks chosen from the posters), two interactive poster sessions and four live software tool demonstrations.
https://www.antibodysociety.org/the-a...
Inferring the differential immunological impact of proton vs photon radiotherapy with TCR sequencing
Dr Jamie Heather
Research Fellow, Massachusetts General Hospital
Radiation therapy has long been a cornerstone of cancer treatment. More recently, immune checkpoint blockade has also been applied across a variety of cancers, often leading to remarkable response rates. However, photon-based radiotherapy – which accounts for the vast majority – is also known to frequently induce profound lymphopenia, which might limit the efficacy of immune system-based combinations. Proton beam therapy is known to produce a less drastic lymphopenia, which raises the possibility of greater synergy with immunotherapy. In this study we aimed to investigate the exact nature of the differential impact of the two radiation modalities upon the immune system. Using multiparametric flow cytometry and deep sequencing of rearranged TCRb loci in a cohort of 20 patients with varying tumors, we explore the nature of the radiation-induced immune dysregulation. Proton-treated patients remained relatively stable across treatment for most metrics considered, whereas those who received photons saw a profound depletion in naïve T cells, increase in effector/memory populations, and loss of TCR diversity. After reaching their lymphocyte count nadir photon-treated patients saw oligoclonal expansion, particularly of CD8+ Temra cells, driving this reduction in diversity. Across the entire cohort, this reduction in post-nadir diversity inversely correlated with the overall survival time of those patients who died. This raises the possibility that increased adoption of proton-based (or other lymphocyte sparing) radiotherapies may lead to better survival in cancer patients.
The meeting covers progress reports from the AIRR-C Working Groups & Sub-committees, two scientific sessions (including four short talks chosen from the posters), two interactive poster sessions and four live software tool demonstrations.
https://www.antibodysociety.org/the-a...
Inferring the differential immunological impact of proton vs photon radiotherapy with TCR sequencing
Dr Jamie Heather
Research Fellow, Massachusetts General Hospital
Radiation therapy has long been a cornerstone of cancer treatment. More recently, immune checkpoint blockade has also been applied across a variety of cancers, often leading to remarkable response rates. However, photon-based radiotherapy – which accounts for the vast majority – is also known to frequently induce profound lymphopenia, which might limit the efficacy of immune system-based combinations. Proton beam therapy is known to produce a less drastic lymphopenia, which raises the possibility of greater synergy with immunotherapy. In this study we aimed to investigate the exact nature of the differential impact of the two radiation modalities upon the immune system. Using multiparametric flow cytometry and deep sequencing of rearranged TCRb loci in a cohort of 20 patients with varying tumors, we explore the nature of the radiation-induced immune dysregulation. Proton-treated patients remained relatively stable across treatment for most metrics considered, whereas those who received photons saw a profound depletion in naïve T cells, increase in effector/memory populations, and loss of TCR diversity. After reaching their lymphocyte count nadir photon-treated patients saw oligoclonal expansion, particularly of CD8+ Temra cells, driving this reduction in diversity. Across the entire cohort, this reduction in post-nadir diversity inversely correlated with the overall survival time of those patients who died. This raises the possibility that increased adoption of proton-based (or other lymphocyte sparing) radiotherapies may lead to better survival in cancer patients.
4 سال پیش
در تاریخ 1399/09/27 منتشر شده
است.
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