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Parameters of Tumor Microenvironment Determine Effectiveness of Anti-PD-1/PD-L1 Therapy
Liubov A Tashireva1, Dariya T Muravyova2, Natalya O Popova2
1Cancer Research Institute, Tomsk National Research Medical Center, Tomsk, 634050, Russia. tashireva@oncology.tomsk.ru.
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.
Insights
Immune checkpoint inhibitors like PD-1/PD-L1 prolong cancer patient survival but do not cure. Tumor microenvironment interactions and immune-inflammatory response (IIR) significantly impact therapy outcomes, including hyperprogressive disease.
Area of Science:
- Oncology
- Immunology
- Cancer Biology
Background:
- Cancer therapy increasingly utilizes pathogenetically based drugs, including immune checkpoint inhibitors targeting PD-1/PD-L1.
- While effective in prolonging survival, these immunotherapies do not consistently cure cancer.
- Tumor cells exploit immune regulatory mechanisms, necessitating a deeper understanding of tumor-microenvironment interactions.
Purpose of the Study:
- To review the complex interactions between tumors and their microenvironment during PD-L1 inhibitor therapy.
- To elucidate the role of the immune-inflammatory response (IIR) in cancer therapy outcomes.
- To explore factors contributing to treatment limitations, such as hyperprogressive disease.
Main Methods:
- Literature review focusing on PD-1/PD-L1 inhibitors and cancer therapy.
- Analysis of tumor-microenvironment dynamics and immune-inflammatory responses.
- Examination of plasticity and adaptive changes within the tumor microenvironment.
Main Results:
- Tumor cell heterogeneity and microenvironment plasticity are key challenges in achieving cures.
- The type of immune-inflammatory response (IIR) within the tumor microenvironment is a critical determinant of therapeutic success.
- Understanding these interactions is crucial for predicting and potentially overcoming treatment resistance and adverse events like hyperprogressive disease.
Conclusions:
- PD-1/PD-L1 inhibitors are valuable but limited by tumor and microenvironment complexity.
- The immune-inflammatory response (IIR) is intrinsically linked to immunotherapy outcomes.
- Further research into tumor-microenvironment dynamics is essential for advancing cancer treatment strategies.
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