14 April 2021: Published today in Nature Communications, the Benvenuti Lab, ICGEB Trieste, identifies how tumours overcome therapy and escape immune surveillance
The holy grails of effective cancer therapy are early diagnosis, prognosis and appropriate forms of therapeutic intervention. In a study led by Federica Benvenuti, Cellular Immunology Group at ICGEB Trieste, in collaboration with laboratories in Italy, China, Japan, Singapore, UK, and the USA, a breakthrough discovery on how the body’s immune response to cancer is perturbed provides compelling evidence for how improved prognosis and tumour therapy can be achieved.
This work has been funded under a grant from AIRC.
A key feature in tumour growth is the loss of immune recognition by the body’s own immune surveillance system. Essential to this are Dendritic Cells which play a critical role in regulating the T cell responses to tumours and which ultimately determines whether a tumour responds to therapy and regresses or not.
The study has defined a key receptor molecule, Tim4, which is essential for Dendritic Cells to be able to optimally present tumour associated antigens to the circulating T cells. In early stage tumours this receptor is highly expressed, and the T cells are concomitantly active against tumour growth. However in late stage cancers this receptor is lost, and the tumour therefore escapes from immune surveillance, ultimately resulting in death of the individual.
This study shows that monitoring the levels of Tim4 expression can offer a very powerful means of early prognosis, which in turn has a major impact on the types of therapeutics that can be applied. In addition, this opens a route for development of novel therapeutic approaches, which aim to restore the body’s own ability to recognize and fight the developing tumour.
Federica Benvenuti comments: “Identification of novel targets for immunotherapy of cancer requires a full understanding of the mechanisms used by innate immune cells to detect the presence of tumor cells and decode their identity.” Further, “in this work we have identified expression of Tim4 on lung resident dendritic cells as critical for acquisition of tumor antigen and initiation of tumor specific T cell responses. Tim4 is downregulated during tumor progression providing a novel mechanism of immune escape and a target to reprogram immunosurveillance.”
Caronni, N., Piperno, G.M., Simoncello, F. et al. TIM4 expression by dendritic cells mediates uptake of tumor-associated antigens and anti-tumor responses. Nat Commun 12, 2237 (2021). https://doi.org/10.1038/s41467-021-22535-z