V-domain Ig suppressor of T cell activation (VISTA) is a
type I transmembrane protein that functions as an
immune checkpoint and is encoded by the ''C10orf54''
gene.
Structure and function
VISTA is approximately 50k
Da and belongs to the
immunoglobulin superfamily and has one
IgV domain.
VISTA is part of the
B7 family, is primarily
expressed in
white blood cell
White blood cells, also called leukocytes or leucocytes, are the cell (biology), cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and de ...
s and its
transcription
Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including:
Genetics
* Transcription (biology), the copying of DNA into RNA, the fir ...
is partially controlled by
p53.
There is evidence that VISTA can act as both a
ligand and a
receptor
Receptor may refer to:
* Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse
*Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a ...
on
T cells to inhibit T cell effector function and maintain
peripheral tolerance
In immunology, peripheral tolerance is the second branch of immunological tolerance, after central tolerance. It takes place in the immune periphery (after T and B cells egress from primary lymphoid organs). Its main purpose is to ensure that ...
.
Clinical significance
VISTA is
produced
Producer or producers may refer to:
Occupations
*Producer (agriculture), a farm operator
*A stakeholder of economic production
*Film producer, supervises the making of films
**Executive producer, contributes to a film's budget and usually does not ...
at high levels in
tumor-infiltrating lymphocytes, such as
myeloid-derived suppressor cells and
regulatory T cells, and its
blockade with an
antibody results in delayed
tumor growth in
mouse
A mouse ( : mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species is the common house mouse (''Mus musculus' ...
models
A model is an informative representation of an object, person or system. The term originally denoted the plans of a building in late 16th-century English, and derived via French and Italian ultimately from Latin ''modulus'', a measure.
Models c ...
of
melanoma
Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye ( ...
and
squamous cell carcinoma
Squamous-cell carcinomas (SCCs), also known as epidermoid carcinomas, comprise a number of different types of cancer that begin in squamous cells. These cells form on the surface of the skin, on the lining of hollow organs in the body, and on the ...
.
s from
HIV-infected
patients produce higher levels of VISTA compared to uninfected individuals. The increased VISTA levels correlated with an increase in immune activation and a
decrease
A decrease in knitting is a reduction in the number of stitches, usually accomplished by suspending the stitch to be decreased from another existing stitch or by knitting it together with another stitch.
Methods of single decreasing (knitting)
Wh ...
in
CD4-positive T cells.
As a drug target
There is an ongoing
cancer immunotherapy clinical trial for a
monoclonal antibody targeting VISTA in
advanced cancer.
Preliminary results of the phase I clinical trial show good safety tolerance and anti-cancer activity in patients with advanced tumours.
Another ongoing clinical trial involves a
small
Small may refer to:
Science and technology
* SMALL, an ALGOL-like programming language
* Small (anatomy), the lumbar region of the back
* ''Small'' (journal), a nano-science publication
* <small>, an HTML element that defines smaller text ...
molecule that
antagonizes the programmed death-ligands 1 and 2 (
PD-L1 and
PD-L2
Programmed cell death 1 ligand 2 (also known as PD-L2, B7-DC) is a protein that in humans is encoded by the ''PDCD1LG2'' gene. PDCD1LG2 has also been designated as CD273 (cluster of differentiation 273). PDCD1LG2 is an immune checkpoint receptor l ...
), and VISTA
pathways in patients with advanced solid tumors or
lymphomas.
References
Further reading
*
*
*
*
External links
*
{{B7 family
Immune system