日本語
 
Help Privacy Policy ポリシー/免責事項
  詳細検索ブラウズ

アイテム詳細


公開

学術論文

Quantification of T- and B-cell immune receptor distribution diversity characterizes immune cell infiltration and lymphocyte heterogeneity in clear cell renal cell carcinoma

MPS-Authors
/persons/resource/persons56574

Altrock,  Philipp M.       
Department Evolutionary Theory (Traulsen), Max Planck Institute for Evolutionary Biology, Max Planck Society;

External Resource
There are no locators available
Fulltext (restricted access)
There are currently no full texts shared for your IP range.
フルテキスト (公開)

929.pdf
(出版社版), 2MB

付随資料 (公開)
There is no public supplementary material available
引用

Ferrall-Fairbanks, M. C., Chakiryan, N., Chobrutskiy, B. I., Kim, Y., Teer, J. K., Berglund, A., Mulé, J. J., Fournier, M., Siegel, E. M., Dhillon, J., Falasiri, S. S. A., Arturo, J. F., Katende, E. N., Blanck, G., Manley, B. J., & Altrock, P. M. (2022). Quantification of T- and B-cell immune receptor distribution diversity characterizes immune cell infiltration and lymphocyte heterogeneity in clear cell renal cell carcinoma. Cancer research: an official organ of the American Association for Cancer Research, 82(5), 929-942. doi:10.1158/0008-5472.CAN-21-1747.


引用: https://hdl.handle.net/21.11116/0000-0009-F997-4
要旨
Immune-modulating systemic therapies are often used to treat advanced cancer such as metastatic clear cell renal cell carcinoma (ccRCC). Used alone, sequence-based biomarkers neither accurately capture patient dynamics nor the tumor immune microenvironment. To better understand the tumor ecology of this immune microenvironment, we quantified tumor infiltration across two distinct ccRCC patient tumor cohorts using complementarity determining region-3 (CDR3) sequence recovery counts in tumor-infiltrating lymphocytes and a generalized diversity index (GDI) for CDR3 sequence distributions. GDI can be understood as a curve over a continuum of diversity scales which allows sensitive characterization of distributions to capture sample richness, evenness, and subsampling uncertainty, along with other important metrics that characterize tumor heterogeneity. For example, richness quantified the total unique sequence count, while evenness quantified similarities across sequence frequencies. Significant differences in receptor sequence diversity across gender and race revealed that patients with larger and more clinically aggressive tumors had increased richness of recovered tumoral CDR3 sequences, specifically in those from T-cell receptor alpha and B-cell immunoglobulin lambda light chain. The GDI inflection point (IP) allowed for a novel and robust measure of distribution evenness. High IP values associated with improved overall survival, suggesting that normal-like sequence distributions lead to better outcomes. These results propose a new quantitative tool that can be used to better characterize patient-specific differences related to immune cell infiltration, and to identify unique characteristics of tumor-infiltrating lymphocyte heterogeneity in ccRCC and other malignancies.