Surprising immune cell discovery may have cancer implications

01 January 2014

T lymphoctyes

Image: Innate-like T lymphocytes.

Scientists have identified a previously unknown subset of T lymphocytes, a type of white blood cell, that can mount a quicker-than-usual response to generic immune threats - termed 'innate-like' immunity.

The findings, by researchers at Cancer Research UK's London Research Institute (LRI; now part of the Francis Crick Institute), King's College London and UCL, have implications for cancer treatment, as innate immune responses can be a crucial part of our defence against the formation of tumours.

Professor Adrian Hayday of LRI explained: "During vaccination or infection by microbes or viruses, T lymphocytes respond to limit infection. These responses are highly specific, targeting very particular pathogens, but are delayed by the time that it takes to assemble the response - typically a week or longer. By contrast, our laboratory has demonstrated that some T lymphocytes react very rapidly to generic signals of something being awry in cells or tissues.

"It's as though T lymphocytes traditionally respond to the presence of a burglar in the house, whereas the subset of T lymphocytes we identified respond to the sight of an open door or broken window, without knowing what caused it.

"Such signs that things are not normal  occur in the early stages of infection by many pathogens. And interestingly, they can also occur in the early stages of cancer, supporting our and others' studies that rapidly-responding T lymphocytes can form one key part of our defences against tumour formation."

Professor Hayday's team used mouse models to investigate the behaviour of the rapidly-responding, innate-like T lymphocytes. The study focused on the very fine dissection of small numbers of cells, using molecular biology and immunology techniques.

They discovered that the 'internal wiring' of the innate-like lymphocytes is altered during development of the cells. This explains how they can behave so differently from conventional lymphocytes - that is, with quick and generic, rather than delayed and specific, responses to immune threats. 

Professor Hayday added: "These findings are important if we are to mobilise innate-like lymphocytes against cancer or if we need to suppress such cells, such as in cases where they may be contributing to inflammatory disease."

He continued: "The journal Science proclaimed cancer immunotherapy as the breakthrough of 2013 and has published clinical studies where conventional T lymphocytes showed efficacy against some solid tumours. However, these may have many severe side-effects and so will need radical refinement before they can be used to treat patients.

"It is likely that innate-like T lymphocytes will form an important part of the immunotherapy arsenal. Any attempts to use them to treat cancer in the clinic should greatly benefit from the improved understanding of their biology provided in this study."

The scientists are now investigating the biology of innate-like T lymphocytes in human samples ranging from normal skin through to primary breast cancers. 

The paper, Innate-like T cells straddle innate and adaptive immunity by revising antigen-receptor responsiveness, is published in Nature Immunology.

  • The discovery of a new subset of T lymphocyte immune cells that can respond more quickly to immune threats may have implications for the treatment of cancer and immune disorders.
  • Innate immune responses have been shown to play a part in defending against certain tumours. And conversely, suppressing innate-like immune responses may be a potential strategy for treating disorders caused by overactive immune responses, such as rheumatoid arthritis and psoriasis.
  • White blood cells are involved in protecting the body against infection and foreign materials. Lymphocytes are one type of these, which are further broken down into large and small lymphocytes. T lymphocytes are one of two types of small lymphocyte, which together with B lymphocytes make up the so-called acquired or adaptive immune system and provide specific responses to threats. There are several types of T lymphocytes, each of which play a distinct role in immunity.
  • Conversely, the innate immune system is comprised of non-lymphocyte types of white blood cell, which provide a non-specific first line of defence.