DrEhsan Ghorani
Clinical Associate Professor in Medical Oncology
Department of Surgery & Cancer - Faculty of Medicine
Orcid identifier0000-0001-5373-5762 (opens in a new tab)
- Clinical Associate Professor in Medical OncologyDepartment of Surgery & Cancer - Faculty of Medicine
- Commonwealth Building, Hammersmith Campus, United Kingdom
RESEARCH
Research
Our lab uses wet lab and computational approaches to understand the immune response to cancer in patients and mouse models. We focus on:
1. Cancer antigen immunogenicity [12].
2. The immune microenvironment of cancer, in particular in relationship to mechanisms of immune function [5, 9], dysfunction [2, 6, 10], the T cell receptor landscape [4], cancer neoantigens as drivers of immune failure [1] and evolution of the immune landscape particularly with respect to CD4 T cell plasticity. Collaborators include Lucy Walker, Benny Chain, Teresa Marafioti and Sergio Quezada (UCL), Khalid AbdulJabbar (ICR) and Rafi Ahmed (Emory University).
3. Mechanisms of anti-PD1 action [13] using samples from patients with gestational cancers, lung and renal cancer. One area we're focussed on is how PD1 receptor occupancy affects T cell function.
4. Application of machine learning (computer vision, novel statistical approaches) to study immune activation using routinely collected patient data (in collaboration with Sarah Filippi)
Key publications
1 Ghorani E, Reading JL, Henry JY, et al. The T cell differentiation landscape is shaped by tumour mutations in lung cancer. Nat cancer 2020;1:546–61. doi:10.1038/s43018-020-0066-y
2 Alrasheed N, Lee L, Ghorani E, et al. Marrow-Infiltrating Regulatory T Cells Correlate with the Presence of Dysfunctional CD4 PD-1 Cells and Inferior Survival in Patients with Newly Diagnosed Multiple Myeloma. Clin Cancer Res 2020;26:3443–54. doi:10.1158/1078-0432.CCR-19-1714
3 Śledzińska A, Vila de Mucha M, Bergerhoff K, et al. Regulatory T Cells Restrain Interleukin-2- and Blimp-1-Dependent Acquisition of Cytotoxic Function by CD4 T Cells. Immunity 2020;52:151-166.e6. doi:10.1016/j.immuni.2019.12.007
4 Joshi K, de Massy MR, Ismail M, et al. Spatial heterogeneity of the T cell receptor repertoire reflects the mutational landscape in lung cancer. Nat Med 2019;25:1549–59. doi:10.1038/s41591-019-0592-2
5 Menares E, Gálvez-Cancino F, Cáceres-Morgado P, et al. Tissue-resident memory CD8 T cells amplify anti-tumor immunity by triggering antigen spreading through dendritic cells. Nat Commun 2019;10:4401. doi:10.1038/s41467-019-12319-x
6 Rosenthal R, Cadieux EL, Salgado R, et al. Neoantigen-directed immune escape in lung cancer evolution. Nature 2019;567:479–85. doi:10.1038/s41586-019-1032-7
7 Wong YNS, Joshi K, Khetrapal P, et al. Urine-derived lymphocytes as a non-invasive measure of the bladder tumor immune microenvironment. J Exp Med 2018;215:2748–59. doi:10.1084/jem.20181003
8 Chakravarthy A, Furness A, Joshi K, et al. Pan-cancer deconvolution of tumour composition using DNA methylation. Nat Commun 2018;9:3220. doi:10.1038/s41467-018-05570-1
9 Arce Vargas F, Furness AJS, Litchfield K, et al. Fc Effector Function Contributes to the Activity of Human Anti-CTLA-4 Antibodies. Cancer Cell 2018;33:649-663.e4. doi:10.1016/j.ccell.2018.02.010
10 Lakins MA, Ghorani E, Munir H, et al. Cancer-associated fibroblasts induce antigen-specific deletion of CD8 T Cells to protect tumour cells. Nat Commun 2018;9:948. doi:10.1038/s41467-018-03347-0
11 Ghorani E, Quezada SA. Chromatin regulation and immune escape. Science 2018;359:745–6. doi:10.1126/science.aat0383
12 Ghorani E, Rosenthal R, McGranahan N, et al. Differential binding affinity of mutated peptides for MHC class I is a predictor of survival in advanced lung cancer and melanoma. Ann Oncol Off J Eur Soc Med Oncol 2018;29:271–9. doi:10.1093/annonc/mdx687
13 Ghorani E, Kaur B, Fisher RA, et al. Pembrolizumab is effective for drug-resistant gestational trophoblastic neoplasia. Lancet 2017;390:2343–5. doi:10.1016/S0140-6736(17)32894-5
Our lab uses wet lab and computational approaches to understand the immune response to cancer in patients and mouse models. We focus on:
1. Cancer antigen immunogenicity [12].
2. The immune microenvironment of cancer, in particular in relationship to mechanisms of immune function [5, 9], dysfunction [2, 6, 10], the T cell receptor landscape [4], cancer neoantigens as drivers of immune failure [1] and evolution of the immune landscape particularly with respect to CD4 T cell plasticity. Collaborators include Lucy Walker, Benny Chain, Teresa Marafioti and Sergio Quezada (UCL), Khalid AbdulJabbar (ICR) and Rafi Ahmed (Emory University).
3. Mechanisms of anti-PD1 action [13] using samples from patients with gestational cancers, lung and renal cancer. One area we're focussed on is how PD1 receptor occupancy affects T cell function.
4. Application of machine learning (computer vision, novel statistical approaches) to study immune activation using routinely collected patient data (in collaboration with Sarah Filippi)
Key publications
1 Ghorani E, Reading JL, Henry JY, et al. The T cell differentiation landscape is shaped by tumour mutations in lung cancer. Nat cancer 2020;1:546–61. doi:10.1038/s43018-020-0066-y
2 Alrasheed N, Lee L, Ghorani E, et al. Marrow-Infiltrating Regulatory T Cells Correlate with the Presence of Dysfunctional CD4 PD-1 Cells and Inferior Survival in Patients with Newly Diagnosed Multiple Myeloma. Clin Cancer Res 2020;26:3443–54. doi:10.1158/1078-0432.CCR-19-1714
3 Śledzińska A, Vila de Mucha M, Bergerhoff K, et al. Regulatory T Cells Restrain Interleukin-2- and Blimp-1-Dependent Acquisition of Cytotoxic Function by CD4 T Cells. Immunity 2020;52:151-166.e6. doi:10.1016/j.immuni.2019.12.007
4 Joshi K, de Massy MR, Ismail M, et al. Spatial heterogeneity of the T cell receptor repertoire reflects the mutational landscape in lung cancer. Nat Med 2019;25:1549–59. doi:10.1038/s41591-019-0592-2
5 Menares E, Gálvez-Cancino F, Cáceres-Morgado P, et al. Tissue-resident memory CD8 T cells amplify anti-tumor immunity by triggering antigen spreading through dendritic cells. Nat Commun 2019;10:4401. doi:10.1038/s41467-019-12319-x
6 Rosenthal R, Cadieux EL, Salgado R, et al. Neoantigen-directed immune escape in lung cancer evolution. Nature 2019;567:479–85. doi:10.1038/s41586-019-1032-7
7 Wong YNS, Joshi K, Khetrapal P, et al. Urine-derived lymphocytes as a non-invasive measure of the bladder tumor immune microenvironment. J Exp Med 2018;215:2748–59. doi:10.1084/jem.20181003
8 Chakravarthy A, Furness A, Joshi K, et al. Pan-cancer deconvolution of tumour composition using DNA methylation. Nat Commun 2018;9:3220. doi:10.1038/s41467-018-05570-1
9 Arce Vargas F, Furness AJS, Litchfield K, et al. Fc Effector Function Contributes to the Activity of Human Anti-CTLA-4 Antibodies. Cancer Cell 2018;33:649-663.e4. doi:10.1016/j.ccell.2018.02.010
10 Lakins MA, Ghorani E, Munir H, et al. Cancer-associated fibroblasts induce antigen-specific deletion of CD8 T Cells to protect tumour cells. Nat Commun 2018;9:948. doi:10.1038/s41467-018-03347-0
11 Ghorani E, Quezada SA. Chromatin regulation and immune escape. Science 2018;359:745–6. doi:10.1126/science.aat0383
12 Ghorani E, Rosenthal R, McGranahan N, et al. Differential binding affinity of mutated peptides for MHC class I is a predictor of survival in advanced lung cancer and melanoma. Ann Oncol Off J Eur Soc Med Oncol 2018;29:271–9. doi:10.1093/annonc/mdx687
13 Ghorani E, Kaur B, Fisher RA, et al. Pembrolizumab is effective for drug-resistant gestational trophoblastic neoplasia. Lancet 2017;390:2343–5. doi:10.1016/S0140-6736(17)32894-5