T lymphocytes against solid malignancies: winning ways to defeat tumours
Authors:Ignazio Caruana1,§, Luca Simula1,2,§, Franco Locatelli1,# and Silvia Campello2,3, #
1 Dept. of Pediatric Onco-Hematology and cell and gene therapy, IRCCS Bambino Gesù Children’s Hospital, Rome, Italy.
2 Dept. of Biology, University of Rome Tor Vergata, Rome, Italy.
3 IRCCS, Santa Lucia Foundation, Rome, Italy.
§,# These authors contributed equally to this work.
Keywords:
cancer immuno-therapy, immune cell infiltration, tumour microenvironment, extracellular matrix, immune-suppression.
Abbreviations:
CAR – chimeric antigen receptor,
DC – dendritic cell,
ECM – extracellular matrix,
ILC – innate lymphoid cell,
MDSC – myeloid-derived suppressor cell,
MHC – major-histocompatibility complex
NK – natural killer,
OXPHOS – oxidative phosphorylation,
SLO – secondary lymphoid organ,
TAMa – tumour-associated macrophage,
TCR – T-cell receptor,
TIL – tumour infiltrating T lymphocytes,
TME – tumour microenvironment,
Treg – regulatory T-cell.
Corresponding Author(s):
Conflict of interest statement:
The authors declare no conflict of interest.
Please cite this article as:
Ignazio Caruana, Luca Simula, Franco Locatelli and Silvia Campello (2018). T lymphocytes against solid malignancies: winning ways to defeat tumours. Cell Stress 2(8): 200-212. doi: 10.15698/cst2018.07.148
© 2018 Caruana et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
Abstract:
In the last decades, a novel field has emerged in the cure of cancer, by boosting the ability of the patient’s immune system to recognize and kill tumour cells. Although excellent and encouraging results, exploiting the effect of genetically modified T cells, have been obtained, it is now evident that tumour malignancies can evolve several mechanisms to escape such immune responses, thus continuing their growth in the body. These mechanisms are in part due to tumour cell metabolic or genetic alterations, which can render the target invisible to the immune system or can favour the generation of an extracellular milieu preventing immune cell infiltration or cytotoxicity. Such mechanisms may also involve the accumulation inside the tumour microenvironment of different immune-suppressive cell types, which further down-regulate the activity of cytotoxic immune cells either directly by interacting with them or indirectly by releasing suppressive molecules. In this review, we will first focus on describing several mechanisms by which tumour cells may dampen or abrogate the immune response inside the tumour microenvironment and, second, on current strategies that are adopted to cope with and possibly overcome such alterations, thus ameliorating the efficacy of the current-in-use anti-cancer immuno-therapies.