The Janus Face of Tumor Microenvironment Targeted by Immunotherapy

International Journal of Molecular Sciences

Maria Buoncervello¹  Elena Toschi¹  Lucia Gabriele² 

[1] Research Coordination and Support Service, Istituto Superiore di Sanità, 00161 Rome, Italy;Tumor Immunology Section, Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, Italy;

关键词: tumor microenvironment (TME);    tumor invasion;    pre-metastatic niche (PMN);    immune cells;    immunotherapy;   

DOI  :  10.3390/ijms20174320

来源: DOAJ

【 摘 要 】

The tumor microenvironment (TME) is a complex entity where host immune and non-immune cells establish a dynamic crosstalk with cancer cells. Through cell-cell interactions, which are mediated by key signals, such as the PD-1/PD-L1 axis, as well as the release of soluble mediators, this articulated process defines the nature of TME determining tumor development, prognosis, and response to therapy. Specifically, tumors are characterized by cellular plasticity that allows for the microenvironment to polarize towards inflammation or immunosuppression. Thus, the dynamic crosstalk among cancer, stromal, and immune components crucially favors the dominance of one of the Janus-faced contexture of TME crucial to the outcome of tumor development and therapeutic response. However, mostly, TME is dominated by an immunosuppressive landscape that blocks antitumor immunity and sustain tumor progression. Hence, in most cases, the immunosuppressive components of TME are highly competent in suppressing tumor-specific CD8⁺ T lymphocytes, the effectors of cancer destruction. In this complex context, immunotherapy aims to arm the hidden Janus face of TME disclosing and potentiating antitumor immune signals. Herein, we discuss recent knowledge on the immunosuppressive crosstalk within TME, and share perspectives on how immunotherapeutic approaches may exploit tumor immune signals to generate antitumor immunity.

【 授权许可】

Unknown