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Parameters of Tumor Microenvironment Determine Effectiveness of Anti-PD-1/PD-L1 Therapy

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Abstract

Undoubtedly, one of the most promising approaches to the treatment of cancer is creation of the pathogenetically based therapeutic drugs. Researchers from all over the world are trying to answer the question on how to select a target that would be effective and, in general, they are quite successful at that. The Nobel Prize-winning discovery of mechanisms for regulating activity of the immune system cells through checkpoint molecules, as well as discovery of the ability of tumor cells to use these mechanisms to suppress immune responses was an impetus for the development of modern immunotherapy, and now such inhibitors of the immune checkpoints as PD-1/PD-L1 are included in the routine chemotherapy. Use of such drugs can prolong the patient’s life, but, unfortunately, not cure the disease. This is partially due to heterogeneity of tumor cells and microenvironment, but the main reasons may be in the complex relationships between the tumor and microenvironment, which, at times, are so plastic that they can change, adjusting to newly emerging conditions. Main characteristic of the tumor microenvironment is the type of the ongoing immune-inflammatory response (IIR), and since inhibitors of the immune checkpoints act on the cells involved in IIR, it is obvious that the outcomes of cancer therapy, including outcomes of hyperprogressive disease, can be associated with this parameter. The presented review reveals the essence of interactions between the tumor and its microenvironment during therapy with PD-L1 inhibitors.

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Abbreviations

BC:

breast carcinoma

CTLA-4:

cytotoxic T-lymphocyte-associated protein 4

HPD:

hyperprogressive disease

IIR:

immune-inflammatory response

IL:

interleukin

NF-κB:

nuclear factor kappa-B

NK cells:

natural killer cells

NSCLC:

non-small cell lung cancer

PD-1:

programmed cell death protein 1

PD-L1:

programmed cell death ligand 1

TILs:

tumor-infiltrating lymphocytes

TNF-α:

tumor necrosis factor-α

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Funding

This work was financially supported by the Russian Science Foundation (project no. 20-75-10033).

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  1. Cancer Research Institute, Tomsk National Research Medical Center, 634050, Tomsk, Russia

    Liubov A. Tashireva, Dariya T. Muravyova, Natalya O. Popova, Victor E. Goldberg, Sergey V. Vtorushin & Vladimir M. Perelmuter

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  1. Liubov A. Tashireva
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  2. Dariya T. Muravyova
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Correspondence to Liubov A. Tashireva.

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Tashireva, L.A., Muravyova, D.T., Popova, N.O. et al. Parameters of Tumor Microenvironment Determine Effectiveness of Anti-PD-1/PD-L1 Therapy. Biochemistry Moscow 86, 1461–1468 (2021). https://doi.org/10.1134/S0006297921110092

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