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Reprogramming the tumor microenvironment to improve the efficacy of cancer immunotherapies

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Abstract

The immunotherapeutic approaches based on checkpoint inhibitors, tumor vaccination, immune cell-based therapy, and cytokines were developed to engage the patient's immune system against cancer and better survival of them. While potent, however, preclinical and clinical data have identified that abnormalities in the tumor microenvironment (TME) can affect the efficacy of immunotherapies in some cancers. It is therefore imperative to develop new therapeutic interventions that will enable to overcome tumor-supportive TME and restrain anti-tumor immunity in patients that acquire resistance to current immunotherapies. Therefore, recognition of the essential nature of the tolerogenic TME may lead to a shift from the immune-suppressive TME to an immune-stimulating phenotype. Here, we review the composition of the TME and its effect on tumor immunoediting and then present how targeted monotherapy or combination therapies can be employed for reprogramming educated TME to improve current immunotherapies outcomes or elucidate potential therapeutic targets.

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Abbreviations

ACT:

Adaptive cell therapies

ADAM:

Activity of disintegrin and metalloproteinase

ADCC:

Antibody-dependent cytotoxicity

CAR-T:

Chimeric antigen receptor T-cell

ECM:

Extracellular matrix

ICB:

Immune checkpoint blockade

MCTs:

Monocarboxylate transporters

TAMs:

Tumor-associated macrophages

TECs:

Tumor-associated ECs

TIL:

Tumor-infiltrating lymphocytes

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Acknowledgements

This study was supported by the Al-Mustaqbal University College, Babylon, Hilla, 51001, Iraq.

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  1. Department of Pharmacy, Al-Mustaqbal University College, Hilla, Babylon, 51001, Iraq

    Jabar A. Faraj, Ali Jihad Hemid Al-Athari, Sharaf El Din Mohie, Iman Kareem Kadhim, Noor Muhsen Jawad & Weaam J. Abbas

  2. Medical Laboratories Techniques Department, Al-Mustaqbal University College, Hilla, Babylon, 51001, Iraq

    Abduladheem Turki Jalil

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  1. Jabar A. Faraj
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Contributions

JAF: Conceptualization, Investigation, Writing—original draft. AJA, SEDM, IKK, NMJ, and WJA: Investigation, Writing—original draft. ATJ: Writing—review & editing, Visualization, Supervision, and Project administration. All co-authors approved the final version of the manuscript.

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Faraj, J.A., Al-Athari, A.H., Mohie, S.E.D. et al. Reprogramming the tumor microenvironment to improve the efficacy of cancer immunotherapies. Med Oncol 39, 239 (2022). https://doi.org/10.1007/s12032-022-01842-5

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