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.