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Litchfield Lab UCL
Group Leader: Dr Kevin Litchfield
Research Overview
Our lab focuses on the genomic and transcriptomic drivers of anti-tumour immune response, using cancer bioinformatics and ex-vivo, in-vivo and in-vitro听experimental approaches.
Immunotherapeutics have led to breakthrough improvements in cancer survival, with immune checkpoint inhibitor (CPI) treatments now approved for over a dozen different tumour types. However, typically only 20-40% of patients benefit from immunotherapy, and novel immune targets are urgently needed to expand the proportion of patients who respond to treatment. An effective anti-tumour immune response is underpinned by multiple factors, including the presence of immunogenic HLA-presented peptides, a functional immune cell infiltration into the tumour core, as well ongoing T-cell priming in tertiary or secondary structures. These processes are regulated by a network of costimulatory molecules, as well as influenced by tumour cell intrinsic events, and hence we adopt a听systems level understanding of immunotherapy response throughout our work.
Experimentally, there are a lack of model systems able to recapitulate the complexity of immunotherapy response, and instead our lab conducts discovery work utilising patient samples from clinical trials. Multi-omic profiling of clinical samples has already enhanced our understanding of immunotherapy activity, establishing for example tumour mutation burden as a key driver of CPI response and hence validating the neoantigen hypothesis. A key capability of听our lab is conducting large-scale integrated analysis of multi-omic datasets, generated directly from patient tumour tissue, in order to identify of the next generation of cancer immunotherapy targets. Working over the last five years we have compiled one of the world鈥檚 largest exome/RNAseq datasets from immunotherapy treated patients. This work is now formalised through an international consortium, with in total genomic/transcriptomic data already available from n=1500 patients, across eight tumour types.
Once novel therapeutic targets are identified听in patient datasets, we then use a combination of听in vitro,听ex vivo听and听in vivo听techniques to explore the functional basis of anti-tumour immune response and develop candidate therapeutic approaches. Biologically,听a key interest of the lab is the听identification of听novel sources of tumour specific antigen capable of eliciting an anti-tumour immune response, as well as characterising cellular pathways which can be perturbed to increase tumour cell immunogenicity.听
Recently published research projects
We recently published a DNA sequencing study in Nature:
听Bentham R, Litchfield K, Watkins TBK, Lim EL, Rosenthal R, Mart铆nez-Ruiz C, Hiley CT, Bakir MA, Salgado R, Moore DA, Jamal-Hanjani M; TRACERx Consortium, Swanton C, McGranahan N.
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We recently published a spatial evolutionary study in Nature Ecology &听Evolution:
听Zhao Y, Fu X, Lopez JI, Rowan A, Au L, Fendler A, Hazell S, Xu H, Horswell S, Shepherd STC, Spain L, Byrne F, Stamp G, O'Brien T, Nicol D, Augustine M, Chandra A, Rudman S, Toncheva A, Pickering L, Sahai E, Larkin J, Bates PA, Swanton C, Turajlic S; TRACERx Renal Consortium,听Litchfield K.听()
We recently published our CPI1000+ meta-analysis dataset in Cell:
. Kevin Litchfield 1, James L Reading 2, Clare Puttick 3, Krupa Thakkar 1, Chris Abbosh 4, Robert Bentham 4, Thomas B K Watkins 3, Rachel Rosenthal 3, Dhruva Biswas 3, Andrew Rowan 3, Emilia Lim 3, Maise Al Bakir 3, Virginia Turati 5, Jos茅 Afonso Guerra-Assun莽茫o 6, Lucia Conde 6, Andrew J S Furness 7, Sunil Kumar Saini 8, Sine R Hadrup 8, Javier Herrero 6, Se-Hoon Lee 9, Peter Van Loo 10, Tariq Enver 5, James Larkin 7, Matthew D Hellmann 11, Samra Turajlic 12, Sergio A Quezada 13, Nicholas McGranahan 14, Charles Swanton 15. Cell. 2021 Feb 4;184(3):596-614.e14. doi: 10.1016/j.cell.2021.01.002. Epub 2021 Jan 27
We have recently published work indentifying the nonsense mediated decay pathway as a key driver of immunotherapy response, and a pathway which can be perturbed to enhance tumour cell immunogenicity:
Litchfield K, Reading JL, Lim EL, Xu H, Liu P, Al-Bakir M, Wong YNS, Rowan A, Funt SA, Merghoub T, Perkins D, Lauss M, Svane IM, J枚nsson G, Herrero J, Larkin J, Quezada SA, Hellmann MD, Turajlic S, Swanton C.听Nat Commun. 2020 Jul 30;11(1):3800. doi: 10.1038/s41467-020-17526-5.听PMID: 32733040
Our Funders
Pancreatic Cancer Research Fund
Previously published research projects
Litchfield K, Reading JL, Lim EL, Xu H, Liu P, Al-Bakir M, Wong YNS, Rowan A, Funt SA, Merghoub T, Perkins D, Lauss M, Svane IM, J枚nsson G, Herrero J, Larkin J, Quezada SA, Hellmann MD, Turajlic S, Swanton C.听Nat Commun. 2020 Jul 30;11(1):3800. doi: 10.1038/s41467-020-17526-5.听PMID: 32733040
Litchfield K, Stanislaw S, Spain L, Gallegos LL, Rowan A, Schnidrig D, Rosenbaum H, Harle A, Au L, Hill SM, Tippu Z, Thomas J, Thompson L, Xu H, Horswell S, Barhoumi A, Jones C, Leith KF, Burgess DL, Watkins TBK, Lim E, Birkbak NJ, Lamy P, Nordentoft I, Dyrskj酶t L, Pickering L, Hazell S, Jamal-Hanjani M; PEACE Consortium, Larkin J, Swanton C, Alexander NR, Turajlic S.听Cell Rep. 2020 May 5;31(5):107550. doi: 10.1016/j.celrep.2020.107550.听PMID: 32375028
听Desiree Schnidrig, Samra Turajlic, Kevin Litchfield.
Wolf Y, Bartok O, Patkar S, Eli GB, Cohen S, Litchfield K, Levy R, Jim茅nez-S谩nchez A, Trabish S, Lee JS, Karathia H, Barnea E, Day CP, Cinnamon E, Stein I, Solomon A, Bitton L, P茅rez-Guijarro E, Dubovik T, Shen-Orr SS, Miller ML, Merlino G, Levin Y, Pikarsky E, Eisenbach L, Admon A, Swanton C, Ruppin E, Samuels Y.听Cell. 2019 Sep 19;179(1):219-235.e21. doi: 10.1016/j.cell.2019.08.032. Epub 2019 Sep 12.
Budczies J, Allg盲uer M, Litchfield K, Rempel E, Christopoulos P, Kazdal D, Endris V, Thomas M, Fr枚hling S, Peters S, Swanton C, Schirmacher P, Stenzinger A.Ann Oncol. 2019 Sep 1;30(9):1496-1506. doi: 10.1093/annonc/mdz205.
Turajlic S*, Xu H*, Litchfield K*, Rowan A, Chambers T, Lopez JI, Nicol D, O'Brien T, Larkin J, Horswell S, Stares M, Au L, Jamal-Hanjani M, Challacombe B, Chandra A, Hazell S, Eichler-Jonsson C, Soultati A, Chowdhury S, Rudman S, Lynch J, Fernando A, Stamp G, Nye E, Jabbar F, Spain L, Lall S, Guarch R, Falzon M, Proctor I, Pickering L, Gore M, Watkins TBK, Ward S, Stewart A, DiNatale R, Becerra MF, Reznik E, Hsieh JJ, Richmond TA, Mayhew GF, Hill SM, McNally CD, Jones C, Rosenbaum H, Stanislaw S, Burgess DL, Alexander NR, Swanton C; PEACE; TRACERx Renal Consortium.听Cell. 2018 Apr 19;173(3):581-594.e12. doi: 10.1016/j.cell.2018.03.057. Epub 2018 Apr 12.
Turajlic S*, Xu H*, Litchfield K*, Rowan A, Horswell S, Chambers T, O'Brien T, Lopez JI, Watkins TBK, Nicol D, Stares M, Challacombe B, Hazell S, Chandra A, Mitchell TJ, Au L, Eichler-Jonsson C, Jabbar F, Soultati A, Chowdhury S, Rudman S, Lynch J, Fernando A, Stamp G, Nye E, Stewart A, Xing W, Smith JC, Escudero M, Huffman A, Matthews N, Elgar G, Phillimore B, Costa M, Begum S, Ward S, Salm M, Boeing S, Fisher R, Spain L, Navas C, Gr枚nroos E, Hobor S, Sharma S, Aurangzeb I, Lall S, Polson A, Varia M, Horsfield C, Fotiadis N, Pickering L, Schwarz RF, Silva B, Herrero J, Luscombe NM, Jamal-Hanjani M, Rosenthal R, Birkbak NJ, Wilson GA, Pipek O, Ribli D, Krzystanek M, Csabai I, Szallasi Z, Gore M, McGranahan N, Van Loo P, Campbell P, Larkin J, Swanton C; TRACERx Renal Consortium.Cell. 2018 Apr 19;173(3):595-610.e11. doi: 10.1016/j.cell.2018.03.043. Epub 2018 Apr 12.
Arce Vargas F, Furness AJS, Litchfield K, Joshi K, Rosenthal R, Ghorani E, Solomon I, Lesko MH, Ruef N, Roddie C, Henry JY, Spain L, Ben Aissa A, Georgiou A, Wong YNS, Smith M, Strauss D, Hayes A, Nicol D, O'Brien T, M氓rtensson L, Ljungars A, Teige I, Frend茅us B; TRACERx Melanoma; TRACERx Renal; TRACERx Lung consortia, Pule M, Marafioti T, Gore M, Larkin J, Turajlic S, Swanton C, Peggs KS, Quezada SA.Cancer Cell. 2018 Apr 9;33(4):649-663.e4. doi: 10.1016/j.ccell.2018.02.010. Epub 2018 Mar 22
Litchfield K, Turajlic S, Swanton C.听Cancer Discov. 2017 Aug;7(8):796-798. doi: 10.1158/2159-8290.CD-17-0604.
Turajlic S*, Litchfield K*, Xu H, Rosenthal R, McGranahan N, Reading JL, Wong YNS, Rowan A, Kanu N, Al Bakir M, Chambers T, Salgado R, Savas P, Loi S, Birkbak NJ, Sansregret L, Gore M, Larkin J, Quezada SA, Swanton C.听Lancet Oncol. 2017 Aug;18(8):1009-1021. doi: 10.1016/S1470-2045(17)30516-8. Epub 2017 Jul 7
Litchfield K, Levy M, Orlando G, Loveday C, Law PJ, Migliorini G, Holroyd A, Broderick P, Karlsson R, Haugen TB, Kristiansen W, Nsengimana J, Fenwick K, Assiotis I, Kote-Jarai Z, Dunning AM, Muir K, Peto J, Eeles R, Easton DF, Dudakia D, Orr N, Pashayan N; UK Testicular Cancer Collaboration; PRACTICAL Consortium, Bishop DT, Reid A, Huddart RA, Shipley J, Grotmol T, Wiklund F, Houlston RS, Turnbull C.听Nat Genet. 2017 Jul;49(7):1133-1140. doi: 10.1038/ng.3896. Epub 2017 Jun 12
Litchfield K, Levy M, Dudakia D, Proszek P, Shipley C, Basten S, Rapley E, Bishop DT, Reid A, Huddart R, Broderick P, Castro DG, O'Connor S, Giles RH, Houlston RS, Turnbull C.听Nat Commun. 2016 Dec 20;7:13840. doi: 10.1038/ncomms13840
Taylor-Weiner A, Zack T, O'Donnell E, Guerriero JL, Bernard B, Reddy A, Han GC, AlDubayan S, Amin-Mansour A, Schumacher SE, Litchfield K, Turnbull C, Gabriel S, Beroukhim R, Getz G, Carter SL, Hirsch MS, Letai A, Sweeney C, Van Allen EM.听Nature. 2016 Nov 30;540(7631):114-118. doi: 10.1038/nature20596
Litchfield K, Holroyd A, Lloyd A, Broderick P, Nsengimana J, Eeles R, Easton DF, Dudakia D, Bishop DT, Reid A, Huddart RA, Grotmol T, Wiklund F, Shipley J, Houlston RS, Turnbull C.听Nat Commun. 2015 Oct 27;6:8690. doi: 10.1038/ncomms9690
Litchfield K, Summersgill B, Yost S, Sultana R, Labreche K, Dudakia D, Renwick A, Seal S, Al-Saadi R, Broderick P, Turner NC, Houlston RS, Huddart R, Shipley J, Turnbull C.听Nat Commun. 2015 Jan 22;6:5973. doi: 10.1038/ncomms6973
