Cytotoxic T lymphocytes (CTLs) are a specialised form of killer cells which are capable of moving around the body, seeking out harmful cells, and removing them from the body before their harmful effects have been felt. It was believed that CTLs arrive at target sites in a random manner or after having being directed there by other leukocytes. However, Niño et al., have discovered that CTLs are in fact capable of swarming to the direct location and themselves signalling to other lymphocytes for their recruitment en masse.
The authors used IonOpticks Aurora Series columns to perform detailed proteomic analysis of the secretome, following the arrival of CTLs at a target. For this, a sophisticated three-dimensional tumouroid was used to mimic the tissue environment of a real tumour. In particular, they determined that once CTLs had recognised their target, they transformed to become ‘engager/recruiter” CTLs that secrete the chemokines CCL3 and CCL4, which are known to be present in the microenvironment of “hot” tumours. As such, any CCR5-expressing CTLs present within the vicinity of the cell will flood to the site, themselves become recruiters, and amplify this chemoattractive signal. This process continues in a positive loop and results in the sustained accumulation of CTLs at the target site.
Read the full paper
Cytotoxic T cells swarm by homotypic chemokine signalling.
Elife. 2020 Oct 13;9:e56554. doi: 10.7554/eLife.56554.
Galeano Niño JL, Pageon SV, Tay SS, Colakoglu F, Kempe D, Hywood J, Mazalo JK, Cremasco J, Govendir MA, Dagley LF, Hsu K, Rizzetto S, Zieba J, Rice G, Prior V, O’Neill GM, Williams RJ, Nisbet DR, Kramer B, Webb AI, Luciani F, Read MN, Biro M.
Commentary by Andrew Webb, PhD.
About the author
Andrew has over 15 years’ experience in the field of chromatography and mass spectrometry. He is the lead innovator and inventor at IonOpticks, working closely with the team to test, refine and develop cutting edge techniques to support higher quality outputs and analytics from MS instruments. Andrew is also the Lab Head of the Walter and Eliza Hall Institute of Medical Research’s Proteomics Research Laboratory.