Article Text

Download PDFPDF
Meltdown of the cold tumour microenvironment: a new ‘translational’ approach to augment immunotherapy efficacy
  1. Alfred Sze-Lok Cheng
  1. School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong
  1. Correspondence to Professor Alfred Sze-Lok Cheng, Rm 406A, Lo Kwee-Seong Integrated Biomedical Sciences Building, Area 39, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China; alfredcheng{at}

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Liver cancer represents a huge global burden as the third leading cause of cancer deaths. While hepatocellular carcinoma accounts for 80%–90% of primary liver cancer diagnoses, the incidence of intrahepatic cholangiocarcinoma (ICC) is increasing in most countries.1 Although the restoration of T cell functions by immune checkpoint inhibitors (ICIs) has achieved unprecedented clinical responses in various malignancies, the role for immunotherapy in ICC remains to be established.1 The heterogeneous ICI responsiveness is influenced by a range of tumour cell-intrinsic factors, tumour-stroma factors including the immunosuppressive tumour microenvironment (TME) and host-related influences such as gut microbiota.2 Despite our improved understanding of the pathophysiology and genetic drivers of ICC,1 this knowledge is yet to be translated into clinical practice. In particular, the desmoplastic ICC has a rich stroma of immunosuppressive myeloid cells, including tumour-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs), which mediate immune escape by impairing T cell activity and proliferation that may undermine response to ICI.3 A major challenge for ICC immunotherapy is therefore the need to turn cold, T cell-dysfunctional tumours into hot, …

View Full Text


  • Contributors AS-LC wrote this commentary.

  • Funding This work is supported partially by the Collaborative Research Fund (C4045-18W), General Research Fund (14115820, 14120621), the Li Ka Shing Foundation and the Strategic Seed Funding for Collaborative Research Scheme (2021-22).

  • Competing interests None declared.

  • Provenance and peer review Commissioned; externally peer reviewed.

Linked Articles