Kellie N. Smith
Unlocking the power of tumor-specific T cells
Associate Professor
Department of Oncology
School of Medicine
Research Overview
Dr. Smith’s lab focuses on defining the functional programming of tumor-specific T cells as it relates to immunotherapy response. While much of her work is in the setting of early stage/resectable lung cancer, she also leads or participates in projects focused on other cancer types, including head and neck cancers, sinonasal carcinoma, Merkel cell carcinoma, mesothelioma, and esophageal cancer. Her lab collaborates 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 early work used a novel approach developed by her lab, called MANAFEST (mutation associated neoantigen functional expansion of specific T-cells) to detect and monitor responses to mutation associated neoantigens, endogenous retroviruses, tumor associated antigens, and viral antigens. More recently, she has used this platform coupled with high dimensional -omics approaches to study the transcriptional programming of tumor-reactive T cells in cancer patients treated with checkpoint blockade. Ongoing work is focused on using innovative murine models to better understand the mechanistic underpinnings of her discoveries in human biospecimens. This work has already led to the identification of new therapeutic targets and mechanisms that are being explored in clinical trial designs.
Selected Publications
- Caushi JX, Zhang J, Ji Z, Vaghasia A, Zhang B, Hsiue EH, 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 P, Choudhury B, Aparicio L, Cheung LS, Lanis M, Belcaid Z, El Asmar M, Illei PB, Wang R, Meyers J, Schuebel 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. Transcriptional programs of neoantigen-specific TIL in anti-PD-1-treated lung cancers. Nature. 2021 Erratum in: 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.
- Dykema AG, Zhang J, Zhang B, Cheung LS, Zeng Z, Cherry CM, Li T, Caushi JX, Nishimoto M, Connor S, Ji Z, Munoz AJ, Hou W, Zhan W, Singh D, Rashid R, Mitchell-Flack M, Bom S, Tam A, Ionta N, Wang Y, Sawosik CA, Tirado LE, Tomasovic LM, Van Dyke D, Spangler JB, Anagnostou V, Yang S, Spicer J, Rayes R, Taube JM, Brahmer JR, Forde PM, Yegnasubramanian S, Ji H, Pardoll DM, Smith KN. Lung tumor-infiltrating Treg have divergent transcriptional profiles and function linked to checkpoint blockade response. Science Immunology. 2023.
- Voong KR, Illei PB, Presson B, Singh D, Zeng Z, Lanis M, Hales RK, Hu C, Tran PT, Georgiades C, Lin CT, Thiboutout J, Brahmer JR, Forde PM, Naidoo J, Anagnostou V, Smith KN. Ablative radiation alone in stage I lung cancer produces an adaptive systemic immune response: insights from a prospective study. Journal of Immunotherapy for Cancer, 2023.
- 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