Abstract A030: Blood-based screening panel for lung cancer based on clonal hematopoietic mutations in tumor infiltrating immune cells

Abstract

Abstract Early detection can significantly reduce mortality due to lung cancer. However, the high cost of the currently approved screening protocol has limited its uptake. Presented here is a blood-based screening panel based on clonal hematopoietic mutations. Mutations in tumor cells that inhibit immune destruction have been extensively studied. However, mutations in immune cells that may prevent an effective anti-tumor immune response remain relatively unstudied. Animal model studies suggest that clonal hematopoietic mutations in tumor infiltrating immune cells can modulate cancer progression, representing potential predictive biomarkers. The goal of this study was to determine if the clonal expansion of these mutations in blood samples could predict the occurrence of lung cancer. We identified a set of 98 potentially pathogenic clonal hematopoietic mutations in tumor infiltrating immune cells. A logistic regression machine learning model based on these mutations correctly classified lung cancer and non-cancer blood samples with 94.12% sensitivity (95% Confidence Interval: 92.20-96.04%) and 85.96% specificity (95% Confidence Interval: 82.98-88.95%) in a test set of 578 lung cancer and 545 non-cancer samples from 18 different cohorts. More importantly, 89.98% of the cancer cases were unambiguously predicted with probability of cancer >0.90 and 74.86% of the non-cancer cases with probability of cancer <0.10. These results suggest that it may be possible to develop an accurate blood-based lung cancer screening panel. Unlike most other “liquid biopsies” currently under development, the assay presented here is based on standard sequencing protocols and uses a relatively small number of rationally selected mutations as predictors. Citation Format: Ramu Anandakrishnan, Ryan Shahidi, Andrew Dai, Veneeth Antony. Blood-based screening panel for lung cancer based on clonal hematopoietic mutations in tumor infiltrating immune cells [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2023 Oct 1-4; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Immunol Res 2023;11(12 Suppl):Abstract nr A030.