Associate Professor
Oncology Department, Johns Hopkins School of Medicine
RESEARCH OVERVIEW
Dr. Smith’s lab focuses on defining the functional programming of tumor-specific CD4+ and CD8+ T cells as it relates to response to immunotherapy. Owing to her interest and expertise in this area, her lab has collaborated with many clinicians within Johns Hopkins and at outside institutions on immunotherapy clinical trials aimed at improving treatment options, preventing disease recurrence, and understanding the predictors of response to treatment in both early and advanced-stage disease.
Dr. Smith’s group has developed a novel patent-pending technique to detect and monitor anti-tumor T cells using a simple liquid biopsy approach. This technique, termed MANAFEST (mutation associated neoantigen functional expansion of specific T-cells), is being used in many clinical trials both within and outside Johns Hopkins and at biotech companies to monitor responses to mutation associated neoantigens, endogenous retroviruses, tumor associated antigens, and viral antigens. Ongoing work includes linking the MANAFEST assay with single cell sequencing technologies to ascertain the intratumoral phenotype of anti-tumor T cells, with a specific interest in how checkpoint blockade treatment regimens augment anti-tumor immunity. This work will elucidate prognostic biomarkers of response and resistance to checkpoint blockade and will help stratify patients most likely to benefit from these treatments.
Cancer Biology | Immunology and Infectious Diseases | Translational Research
Selected Publications
Caushi JX, Zhang J, Ji Z, Vaghasia A, Zhang B, EHC Hsiue, Mog BJ, Hou W, Justesen S, Blosser R, Tam A, Anagnostou V, Cottrell TR, Guo H, Chan HY, Singh D, Thapa S, Dykema AG, Burman Poromendro, Choudhury B, Aparicio L, Cheung LS, Lanis M, Belcaid Z, El Asmar M, Illei PB, Wang R, Meyers J, Scheubel K, Gupta A, Skaist A, Wheelan S, Naidoo J, Marrone KA, Brock M, Ha J, Bush EL, Park BJ, Bott M, Jones DR, Reuss JE, Velculescu VE, Chaft JE, Kinzler KW, Zhou S, Vogelstein B, Taube JM, Hellmann MD, Brahmer JR, Merghoub T, Forde PM, Yegnasubramanian S, Ji H, Pardoll DM, Smith KN. Distinct transcriptional programs characterize neoantigen-specific TIL in lung cancers treated with anti-PD-1. Nature, 2021.
Zhang J, Ji Z, Caushi JX, El Asmar M, Anagnostou V, Cottrell TR, Chan HY, Suri P, Merghoub T, Chaft JE, Reuss JE, Tam AJ, Blosser RL, Abu-Akeel M, Sidhom JW, Zhao N, Ha JS, Jones DR, Marron KA, Naidoo J, Gabrielson E, Taube JM, Velculescu VE, Brahmer JR, Housseau F, Hellmann MD, Forde PM, Pardoll DM, Ji H, Smith KN. Compartmental analysis of T cell clonal dynamics as a function of pathologic response to neoadjuvant PD-1 blockade in resectable non-small cell lung cancer. Clinical Cancer Research, 2020.
Smith KN, Llosa NJ, Cottrell TR, Siegel N, Fan H, Suri P, Chan HY, Guo H, Oke T, Awan AH, Verde F, Danilova L, Anagnostou V, Tam AJ, Luber BS, Bartlett BR, Aulakh LK, Sidhom JW, Zhu Q, Sears CL, Cope L, Sharfman WH, Thompson ED, Riemer J, Marrone KA, Naidoo J, Velculescu VE, Forde PM, Vogelstein B, Kinzler KW, Papadopoulos N, Durham JN, Wang H, Le DT, Justesen S, Taube JM, Diaz LA Jr, Brahmer JR, Pardoll DM, Anders RA, Housseau F. Persistent mutant oncogene specific T cells in two patients benefitting from anti-PD-1. Journal for Immunotherapy of Cancer, 2019.
Danilova L, Anagnostou V, Caushi JX, Sidhom J, Guo H, Chan HY, Suri P, Tam A, Zhang J, El Asmar M, Marrone KA, Naidoo J, Brahmer JR, Forde PM, Baras AS, Cope L, Velculescu VE, Pardoll DM, Housseau F, Smith KN. The mutation associated neoantigen functional expansion of specific T cell receptor clonotypes (MANAFEST) assay: a sensitive platform for monitoring anti-tumor immunity. Cancer Immunology Research, 2018.
Forde PM*, Chaft JE*, Smith KN*, Anagnostou V, Cottrell TR, Hellmann MD, Zahurak M, Yang SC, Jones DR, Broderick S, Battafarano RJ, Velez MJ, Rekhtman N, Olah Z, Naidoo J, Marrone KA, Verde F, Guo H, Zhang J, Caushi JX, Chan HY, Sidhom J, Scharpf RB, White J, Gabrielson E, Wang H, Rosner GL, Rusch V, Wolchok JD, Merghoub T, Taube JM, Velculescu VE, Topalian SL, Brahmer JR, Pardoll DM. Neoadjuvant PD-1 blockade in resectable lung cancer. New England Journal of Medicine, 2018. *Joint authorship