Immunosuppression in tumor immune microenvironment and its optimization from CAR-T cell therapy

Abstract

Chimeric antigen receptor (CAR)-T cell therapy represents a landmark advance in personalized cancer treatment. CAR-T strategy generally engineers T cells from a specific patient with a new antigen-specificity, which has achieved considerable success in hematological malignancies, but scarce benefits in solid tumors. Recent studies have demonstrated that tumor immune microenvironment (TIME) cast a profound impact on the immunotherapeutic response. The immunosuppressive landscape of TIME is a critical obstacle to the effector activity of CAR-T cells. Nevertheless, every cloud has a silver lining. The immunosuppressive components also shed new inspiration on reshaping a friendly TIME by targeting them with engineered CARs. Herein, we summarize recent advances in disincentives of TIME and discuss approaches and technologies to enhance CAR-T cell efficacy via addressing current hindrances. Simultaneously, we firmly believe that by parsing the immunosuppressive components of TIME, rationally manipulating the complex interactions of immunosuppressive components, and optimizing CAR-T cell therapy for each patient, the CAR-T cell immunotherapy responsiveness for solid malignancies will be substantially enhanced, and novel therapeutic targets will be revealed.

Pathways of Angiogenic and Inflammatory Cytokines in Multiple Myeloma: Role in Plasma Cell Clonal Expansion and Drug Resistance

“…Several studies have endeavored to integrate chemokines and CAR-T cells to fight cancer, with ongoing investigations focused on CXCR2-modified CAR-T cells that have been shown to induce complete tumour regression and immunological memory in aggressive tumors [ 130 ].…”

The deubiquitinating enzyme MINDY2 promotes pancreatic cancer proliferation and metastasis by stabilizing ACTN4 expression and activating the PI3K/AKT/mTOR signaling pathway

“…In recent years, tumor immunotherapy has become a hot spot in the eld of tumor treatment research and is also considered one of the most promising treatment methods. Immunotherapy has achieved great success in the treatment of many tumors [37]; however, its therapeutic effect in PC is minimal [38]. In this study, we analyzed the correlation between MINDY2 in PC and immunity and found that MINDY2 was signi cantly and positively correlated with in ltration scores of B cells, T cells CD8+, neutrophil, macrophage, and myeloid dendritic cells in PC, and although there was no statistical signi cance between MINDY2 and T cells CD4+, it can be concluded that the expression level of CD4 + T cells was greater in the MINDY2 high expression group than in the low expression group.…”

Relationship between Osteosarcoma Therapy and Tumorigenesis, Metastasis, Immune Evasion, and Chemoresistance

“…Tumour cells escape being destroyed by the immune system because the immune cells, such as neutrophils, monocytes, macrophages, dendritic cells, natural killer cells, and B and T lymphocytes, are suppressed [138]. Besides, the tumour immune responses are barred from immune checkpoint activations, thereby causing immune evasion [139]. Therefore, the immune evasion is eliminated by suppressing and inhibiting the both mechanisms.…”