Cancer Stem Cells Are Possible Key Players in Regulating Anti-Tumor Immune Responses: The Role of Immunomodulating Molecules and MicroRNAs

Abstract

Cancer cells endowed with stemness properties and representing a rare population of cells within malignant lesions have been isolated from tumors with different histological origins. These cells, denominated as cancer stem cells (CSCs) or cancer initiating cells (CICs), are responsible for tumor initiation, progression and resistance to therapies, including immunotherapy. The dynamic crosstalk of CSCs/CICs with the tumor microenvironment orchestrates their fate and plasticity as well as their immunogenicity. CSCs/CICs, as observed in multiple studies, display either the aberrant expression of immunomodulatory molecules or suboptimal levels of molecules involved in antigen processing and presentation, leading to immune evasion. MicroRNAs (miRNAs) that can regulate either stemness properties or their immunological profile, with in some cases dual functions, can provide insights into these mechanisms and possible interventions to develop novel therapeutic strategies targeting CSCs/CICs and reverting their immunogenicity. In this review, we provide an overview of the immunoregulatory features of CSCs/CICs including miRNA profiles involved in the regulation of the interplay between stemness and immunological properties.

Integrated Analysis of Stemness-Related LncRNAs Helps Predict the Immunotherapy Responsiveness of Gastric Cancer Patients

“…Considering that only 29 cases were included in the Zhongshan cohort, it was not enough to make people believe that the signature could serve as an effective predictor of chemotherapy. Notably, stemness has also been reported to be associated with immunotherapy in recent published literatures ( Vodnala et al, 2019 ; Hadadi et al, 2020 ; Ishii et al, 2021 ; Tomei et al, 2021 ; Wang et al, 2021 ). It prompted us to explore the relevance between the SRLncSig and immunotherapy.…”

Cancer stem cell, chromosomal instability, and cancer immunity

“…T cells exert an immune response after recognizing antigens presented by antigen-presenting cells and nonimmune cells. MHC I presents an antigen that is identified by CD8 + T cell receptor (TCR) [98]. Full activation of T cells requires TCR signaling and secondary signaling through costimulatory molecules.…”

Immunobiology of cancer stem cells and their immunoevasion mechanisms

“…They express different patterns of markers in accordance with their phenotypes and the microenvironment they survive. However, the most common biomarkers in this population include membrane-bound antigens, such as CD44, CD24, CD133, CD34, and CD38 and cytoplasmic enzymes like ALDH1 [11]. Nevertheless, nding a highly speci c and comprehensive biomarker for diagnosing CSCs remains unanswered and needs further researches.…”

“…Intriguingly, three important signaling pathways, namely Notch, Wnt/β-catenin, and Hh have wide range of functions in both CSCs and immune cells, which makes them hot topics for many researches [8,10]. Since they not only play multitude roles in differentiation and maturation of distinct immune cells, but also regulate selfreplication and immune avoidance potential in CSCs [10,11,15]. In accordance with this point, many other overlaps have been mentioned in the context of regulatory markers and signaling pro le.…”

“…Neoantigens originated from somatic mutations in cancer cells which are tumor speci c and completely novel for immune system, iv. Tissue differentiation antigens expressed in both normal and cancer cells (like MART-1 in melanoma, PSA in prostate cancer) [1,10,11].…”