Expression of immune checkpoints PD-L1, CTLA4, LAG3 in the microenvironment of colon adenocarcinoma depending on MMR status

Naumov S.S.

Siberian State Medical University

ORCID: 0000-0003-3868-2310

Krakhmal N.V.

Siberian State Medical University;
Cancer Research Institute — Tomsk National Research Medical Center of the Russian Academy of Sciences

ORCID: 0000-0002-1909-1681

Tashireva L.A.

Cancer Research Institute — Tomsk National Research Medical Center of the Russian Academy of Sciences

ORCID: 0000-0003-2061-8417

Vtorushin S.V.

Siberian State Medical University;
Cancer Research Institute — Tomsk National Research Medical Center of the Russian Academy of Sciences

ORCID: 0000-0002-1195-4008

Expression of immune checkpoints PD-L1, CTLA4, LAG3 in the microenvironment of colon adenocarcinoma depending on MMR status

Authors:

Naumov S.S., Krakhmal N.V., Tashireva L.A., Vtorushin S.V.

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Journal: Russian Journal of Archive of Pathology. 2024;86(2): 6‑13

DOI: 10.17116/patol2024860216

Downloaded: 114

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To cite this article:

Naumov SS, Krakhmal NV, Tashireva LA, Vtorushin SV. Expression of immune checkpoints PD-L1, CTLA4, LAG3 in the microenvironment of colon adenocarcinoma depending on MMR status. Russian Journal of Archive of Pathology. 2024;86(2):6‑13. (In Russ.)
https://doi.org/10.17116/patol2024860216

Подписка 2025 (Russian Journal of Archive of Pathology)

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OBJECTIVE

Study of the features of expression of immune checkpoint proteins PD-L1, CTLA4 and LAG3 in the microenvironment of colon adenocarcinoma depending on MMR status.

MATERIAL AND METHODS

The study group consisted of 32 patients with a morphologically confirmed diagnosis of colon cancer; all of them underwent surgical treatment in the form of hemicolonectomy or resection. The work assessed samples of tumor tissue obtained as a result of surgery, the study was carried out in 3 stages: morphological examination of histological slides of colon tumors at the light-optical level, immunohistochemistry examination of tumor samples to determine the dMMR/pMMR status of carcinoma using a panel of antibodies to proteins of the unpaired nucleotide repair system MLH1, MSH2, MSH6 and PMS2, multiplex analysis of PD-L1, CTLA4, LAG3, CD3+, CD8+, CD163+ markers using the Vectra 3.0.3 tissue scanning system (Perkin Elmer, USA).

RESULTS

Significant differences in the expression of PD-L1, CTLA4, LAG3 in the area of the invasive tumor margin were revealed between the dMMR and pMMR groups of colon adenocarcinomas in patients comparable in clinical and morphological characteristics and treatment. In the group of tumors with dMMR status, an increase in the expression of all studied markers was noted. The number of CD3+ TILs was also significantly higher in the invasive margin of tumors with dMMR status. Similarly, in this group of colon carcinomas, a large number of CD163+ macrophages were noted both in the center and in the invasive margin zone. No statistically significant differences were found in the expression of immune checkpoints and the composition of TILs in the central zone of tumors with different MMR status.

CONCLUSION

A study using multiplex immunohistochemical analysis showed that MMR-deficient colon adenocarcinomas are characterized by more pronounced immune infiltration and increased expression of immune checkpoints in microenvironmental cells, mainly in the area of invasive tumor growth. The data obtained may be important for understanding the mechanisms of immune-mediated control of tumor growth and the choice of immunotherapy tactics depending on MMR status.

Keywords:

colon adenocarcinoma

PD-L1

CTLA4

LAG3

MMR status

tumor microenvironment

Authors:

Naumov S.S.

Siberian State Medical University

ORCID: 0000-0003-3868-2310

Krakhmal N.V.

Siberian State Medical University;
Cancer Research Institute — Tomsk National Research Medical Center of the Russian Academy of Sciences

ORCID: 0000-0002-1909-1681

Tashireva L.A.

Cancer Research Institute — Tomsk National Research Medical Center of the Russian Academy of Sciences

ORCID: 0000-0003-2061-8417

Vtorushin S.V.

Siberian State Medical University;
Cancer Research Institute — Tomsk National Research Medical Center of the Russian Academy of Sciences

ORCID: 0000-0002-1195-4008

Received:

20.12.2023

Accepted:

27.12.2023

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