The Cross Talk between Cancer Stem Cells/Cancer Initiating Cells and Tumor Microenvironment: The Missing Piece of the Puzzle for the Efficient Targeting of these Cells with Immunotherapy

Saad Rasool,Cristina Maccalli,Shilpa Ravindran

doi:10.1007/s12307-019-00233-1

Abstract

Cancer Stem Cells/Cancer Initiating Cells (CSCs/CICs) is a rare sub-population within a tumor that is responsible for tumor formation, progression and resistance to therapies. The interaction between CSCs/CICs and tumor microenvironment (TME) can sustain “stemness” properties and promote their survival and plasticity. This cross-talk is also pivotal in regulating and modulating CSC/CIC properties. This review will provide an overview of the mechanisms underlying the mutual interaction between CSCs/CICs and TME. Particular focus will be dedicated to the immunological profile of CSCs/CICs and its role in orchestrating cancer immunosurveillance. Moreover, the available immunotherapy strategies that can target CSCs/CICs and of their possible implementation will be discussed. Overall, the dissection of the mechanisms regulating the CSC/CIC-TME interaction is warranted to understand the plasticity and immunoregulatory properties of stem-like tumor cells and to achieve complete eradications of tumors through the optimization of immunotherapy.

Highlights

Tumors are composed by heterogeneous cellular components including a rare subpopulation bearing “stemness properties” and being responsible of tumor initiation and progression
Neoantigens have been described as candidate Tumor associated antigens (TAAs) efficiently recognized by T cells that can be exploited for adoptive cell therapy (ACT) of cancer patients and, interestingly, cytotoxic T lymphocytes (CTLs) targeting these antigens could be isolated from tumor infiltrating lymphocytes (TILs) of melanoma and other type of malignant lesions [183, 185, 186]
Recent advances in the genomic, molecular and immunological profiling of cancer stem cells (CSCs)/cancer initiating cells (CICs) have contributed to the identification of dysregulated molecular pathways that orchestrate stem-like cancer cells and their interaction with tumor microenvironment (TME)

Summary

Introduction

Tumors are composed by heterogeneous cellular components including a rare subpopulation bearing “stemness properties” and being responsible of tumor initiation and progression. The side population (SP) cells derived from CRC and endowed with stemness properties, showed detectable level of HLA class I molecules as well susceptibility to antigen-specific cytotoxic T lymphocytes (CTLs) [71], this study has been performed using long-term in vitro established cell lines, that could have lost phenotypic properties of primary CSCs/CICs. stem-like cells isolated by sphere-forming assay displayed aberrant expression of HLA class I and APM components [16, 65].

Results

Conclusion