Three-dimensional cell models for studying tumor–immune interactions and testing immunotherapeutic drugs

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Abstract

One of the most promising approaches to cancer treatment is immunotherapy. Suppression of immune checkpoints in tumor tissue (anti-CTLA4, anti-PD1) using monoclonal antibodies has increased the overall survival of patients with some forms of skin melanoma and lung cancer. However, the percentage of patients responding to treatment varies from 20% to 40% depending on the type of cancer and the expression of target molecules by the tumor. The main source of failure of immunotherapy is the tumor microenvironment, which affects both tumor cells and immune cells, causing them to adapt to immunotherapeutic drugs. It is known that the architecture and cellular composition of the microenvironment act on various tumor parameters, promoting the recruitment of immunosuppressive cells into the tumor tissue, as well as the expression of checkpoint inhibitors, such as PD-L1, by tumor cells. Therefore, the complex composition of the tumor microenvironment must be taken into account when searching for new therapies and stratifying patients who may respond to immunotherapy. Therefore, in immunooncological studies, it is necessary to use three-dimensional cellular models that more fully reflect the architecture and cellular composition of the tumor. In this review, we evaluate three-dimensional cell models as tools for research in the field of immuno-oncology, as well as for personalized treatment selection, the search for new targets, and the optimization of existing cancer immunotherapies.

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About the authors

Svetlana Yu. Filippova

National medical research centre for Oncology

Author for correspondence.
Email: filsv@yandex.ru
ORCID iD: 0000-0002-4558-5896
SPIN-code: 9586-2785

Research Associate

Russian Federation, 14 liniya street, 63, 344037 Rostov-on-Don

Sophia V. Timofeeva

National medical research centre for Oncology

Email: timofeeva.sophia@gmail.com
ORCID iD: 0000-0002-5945-5961
SPIN-code: 5362-1915

Research Associate

Russian Federation, 14 liniya street, 63, 344037 Rostov-on-Don

Irina V. Mezhevova

National medical research centre for Oncology

Email: mezhevova88@gmail.com
ORCID iD: 0000-0002-7902-7278
SPIN-code: 3367-1741

Junior Research Associate

Russian Federation, 14 liniya street, 63, 344037 Rostov-on-Don

Elena V. Shalashnaya

National medical research centre for Oncology

Email: rnioi@list.ru
ORCID iD: 0000-0001-7742-4918
SPIN-code: 2752-0907

Cand.  Sci. (Bio.)

Russian Federation, 14 liniya street, 63, 344037 Rostov-on-Don

Lyudmila Ya. Rozenko

National medical research centre for Oncology

Email: onko-sekretar@mail.ru
ORCID iD: 0000-0001-7032-8595
SPIN-code: 8879-2251

MD, Dr. Sci. (Med.), Professor

Russian Federation, 14 liniya street, 63, 344037 Rostov-on-Don

Aleksandr V. Shaposhnikov

National medical research centre for Oncology

Email: onko-sekretar@mail.ru
ORCID iD: 0000-0001-6881-2281
SPIN-code: 8756-9438

MD, Dr. Sci. (Med.), Professor

Russian Federation, 14 liniya street, 63, 344037 Rostov-on-Don

Inna A. Novikova

National medical research centre for Oncology

Email: novikovainna@yahoo.com
ORCID iD: 0000-0002-6496-9641
SPIN-code: 4810-2424

MD, Dr. Sci. (Med.)

Russian Federation, 14 liniya street, 63, 344037 Rostov-on-Don

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Supplementary files

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2. Fig. 1. Schematic overview of 3D in vitro models and their application in studies of immune relationships in the tumor microenvironment.

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3. Fig. 2. The process of creating three-dimensional cell cultures to model the relationship between tumor and immunity: a — obtaining a model based on multicellular spheroids co-cultivated with immune cells; b — growing organoids and tumoroids from tumor tissue in biogel followed by co-cultivation with autologous immune cells.

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4. Fig. 3. Obtaining a three-dimensional model of the tumor microenvironment by connecting various components of the model on microfluidic systems (chips).

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5. Fig. 4. Scheme for obtaining a model of the tumor microenvironment using 3D bioprinting.

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