Biophysicochemical Motifs in TCR Antigen Binding Regions as Potential Biomarkers of Cancer
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2 سال پیش
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AIRR Community FOCiS 2021 SymposiumBiophysicochemical
AIRR Community FOCiS 2021 Symposium
Biophysicochemical Motifs in T Cell Receptor Antigen Binding Regions as Potential Biomarkers of Cancer
Lindsay Cowell, University of Texas Southwestern Medical Center, USA
Abstract: Deep sequencing of adaptive immune receptor repertoires (AIRRs) has long been considered a useful tool for the prognostication of cancer patients and the monitoring of immunotherapy responses. We hypothesized that AIRR sequencing may also enable early detection of cancer by detecting T cell receptors (TCRs) that are part of the antitumor immune response. To this end, we compared tumor and healthy tissue repertoires and identified biophysicochemical motifs that distinguish early stage breast cancer repertoires from healthy breast tissue repertoires, colorectal cancer repertoires from healthy colorectal tissue repertoires, and high grade serous ovarian cancer repertoires from the ovarian repertoires of cancer-free women with accuracies ranging from 93-95%. We have shown that the breast cancer motifs can be found in the blood of breast cancer patients. The motifs identified for the three cancer types are distinct, suggesting that they could not only indicate the presence of cancer but also point to the cancer type. Using cervical cancer as a source of pre-neoplasic lesions, we have also demonstrated motifs that predict the likelihood of spontaneous lesion regression.
Speaker Bio: Dr. Lindsay Cowell is an Associate Professor in the Department of Population and Data Sciences and the Department of Immunology at UT Southwestern Medical Center. She is broadly interested in understanding the mechanisms of adaptive immunity and their role in infectious diseases, autoimmune diseases, cancer, and vaccine responses. Research in the Cowell group is currently directed toward advancing understanding of (1) the molecular mechanisms by which adaptive immune receptor genes are somatically generated and diversified, (2) the role of these mechanisms in disease, and (3) the dynamics of adaptive immune receptor repertoires in the context of various states of human health and disease. In addition to our basic science research, the group has pursued clinical applications in the areas of autoimmune disease (e.g., multiple sclerosis), infectious disease (e.g.,Staphylococcus aureus), and cancer (e.g., ovarian cancer, HPV-related cancers, particularly cervical cancer, and design of chimeric antigen receptors for cancer therapy).
Dr. Cowell is the Chair of the AIRR-C Executive Sub-committee and the former Co-lead of the AIRR-C Common Repository Working Group.
Biophysicochemical Motifs in T Cell Receptor Antigen Binding Regions as Potential Biomarkers of Cancer
Lindsay Cowell, University of Texas Southwestern Medical Center, USA
Abstract: Deep sequencing of adaptive immune receptor repertoires (AIRRs) has long been considered a useful tool for the prognostication of cancer patients and the monitoring of immunotherapy responses. We hypothesized that AIRR sequencing may also enable early detection of cancer by detecting T cell receptors (TCRs) that are part of the antitumor immune response. To this end, we compared tumor and healthy tissue repertoires and identified biophysicochemical motifs that distinguish early stage breast cancer repertoires from healthy breast tissue repertoires, colorectal cancer repertoires from healthy colorectal tissue repertoires, and high grade serous ovarian cancer repertoires from the ovarian repertoires of cancer-free women with accuracies ranging from 93-95%. We have shown that the breast cancer motifs can be found in the blood of breast cancer patients. The motifs identified for the three cancer types are distinct, suggesting that they could not only indicate the presence of cancer but also point to the cancer type. Using cervical cancer as a source of pre-neoplasic lesions, we have also demonstrated motifs that predict the likelihood of spontaneous lesion regression.
Speaker Bio: Dr. Lindsay Cowell is an Associate Professor in the Department of Population and Data Sciences and the Department of Immunology at UT Southwestern Medical Center. She is broadly interested in understanding the mechanisms of adaptive immunity and their role in infectious diseases, autoimmune diseases, cancer, and vaccine responses. Research in the Cowell group is currently directed toward advancing understanding of (1) the molecular mechanisms by which adaptive immune receptor genes are somatically generated and diversified, (2) the role of these mechanisms in disease, and (3) the dynamics of adaptive immune receptor repertoires in the context of various states of human health and disease. In addition to our basic science research, the group has pursued clinical applications in the areas of autoimmune disease (e.g., multiple sclerosis), infectious disease (e.g.,Staphylococcus aureus), and cancer (e.g., ovarian cancer, HPV-related cancers, particularly cervical cancer, and design of chimeric antigen receptors for cancer therapy).
Dr. Cowell is the Chair of the AIRR-C Executive Sub-committee and the former Co-lead of the AIRR-C Common Repository Working Group.
2 سال پیش
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