Cancer Stem Cell-Associated Immune Microenvironment in Recurrent Glioblastomas

Cells. 2022 Jun 28;11(13):2054. doi: 10.3390/cells11132054.

Abstract

Glioblastoma multiforme (GBM) is the most incurable tumor (due to the difficulty in complete surgical resection and the resistance to conventional chemo/radiotherapies) that displays a high relapse frequency. Cancer stem cells (CSCs) have been considered as a promising target responsible for therapy resistance and cancer recurrence. CSCs are known to organize a self-advantageous microenvironment (niche) for their maintenance and expansion. Therefore, understanding how the microenvironment is reconstructed by the remaining CSCs after conventional treatments and how it eventually causes recurrence should be essential to inhibit cancer recurrence. However, the number of studies focusing on recurrence is limited, particularly those related to tumor immune microenvironment, while numerous data have been obtained from primary resected samples. Here, we summarize recent investigations on the immune microenvironment from the viewpoint of recurrent GBM (rGBM). Based on the recurrence-associated immune cell composition reported so far, we will discuss how CSCs manipulate host immunity and create the special microenvironment for themselves to regrow. An integrated understanding of the interactions between CSCs and host immune cells at the recurrent phase will lead us to develop innovative therapies and diagnoses to achieve GBM eradication.

Keywords: cancer stem cell; glioblastoma; immune microenvironment; recurrence.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Glioblastoma* / pathology
  • Humans
  • Neoplasm Recurrence, Local / pathology
  • Neoplastic Stem Cells / pathology
  • Stem Cell Niche
  • Tumor Microenvironment

Grants and funding

This work was supported by JSPS Grant-in-Aid for Scientific Research (B) (18H02678) (T.T.), Project for Cancer Research and Therapeutic Evolution (P-CREATE) from the Japan Agency for Medical Research and Development (AMED) (20cm0106264h0002) and JSPS Grant-in-Aid for the Fostering Joint International Research (A) (18KK0433), JSPS Grant-in-Aid for Challenging Exploratory Research (20K21540) (K.T.) and Nanken-Kyoten, TMDU (K.T., Y.M. and T.T.).