Imperial College London

DrEhsanGhorani

Faculty of MedicineDepartment of Surgery & Cancer

Honorary Clinical Research Fellow
 
 
 
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Contact

 

e.ghorani

 
 
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Location

 

Commonwealth BuildingHammersmith Campus

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Summary

 

Research

Ehsan's work focusses on multiomic and high dimensional approaches to understanding the immune response to cancer in patients and mouse models. His recent work has focussed on:

1. Cancer antigen immunogenicity using a novel measure of difference-from-self [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] and cancer neoantigens as drivers of immune failure [1].

3. The anti-PD1 agent pembrolizumab as a cure for rare gestational tumours and mechanistic aspects of its action [13].

Ongoing work is focussed on:

1. Application of machine learning approaches to study immune activation using routinely collected patient data.

2. Combining high dimensional flow cytometry, single cell RNA and TCR sequencing to understand the phenomenon of partial tumour control.

3. Mechanisms of anti-PD1 activity and in particular the effect of dose frequency on T cell function.

Key publications

show research

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