TY - JOUR

T1 - Development of Ex Vivo Analysis for Examining Cell Composition, Immunological Landscape, Tumor and Immune Related Markers in Non-Small-Cell Lung Cancer

AU - Ufimtseva, Elena G.

AU - Gileva, Margarita S.

AU - Kostenko, Ruslan V.

AU - Kozlov, Vadim V.

AU - Gulyaeva, Lyudmila F.

N1 - This work was financially supported by the Russian Science Foundation (grant No. 22-15-00065, \u201CSearch for new targets for the diagnosis and therapy of squamous cell lung cancer\u201D). This work was performed using the equipment of the Centers for Collective Use \u201CSpectrometric Measurements\u201D and \u201CProteomic Analysis\u201D, supported by funding from the Ministry of Science and Higher Education of the Russian Federation (agreement No. 075-15-2021-691).

PY - 2024/8/20

Y1 - 2024/8/20

N2 - NSCLC is a very aggressive solid tumor, with a poor prognosis due to post-surgical recurrence. Analysis of the specific tumor and immune signatures of NSCLC samples is a critical step in prognostic evaluation and management decisions for patients after surgery. Routine histological assays have some limitations. Therefore, new diagnostic tools with the capability to quickly recognize NSCLC subtypes and correctly identify various markers are needed. We developed a technique for ex vivo isolation of cancer and immune cells from surgical tumor and lung tissue samples of patients with NSCLC (adenocarcinomas and squamous cell carcinomas) and their examination on ex vivo cell preparations and, parallelly, on histological sections after Romanovsky–Giemsa and immunofluorescent/immunochemical staining for cancer-specific and immune-related markers. As a result, PD-L1 expression was detected for some patients only by ex vivo analysis. Immune cell profiling in the tumor microenvironment revealed significant differences in the immunological landscapes between the patients’ tumors, with smokers’ macrophages with simultaneous expression of pro- and anti-inflammatory cytokines, neutrophils, and eosinophils being the dominant populations. The proposed ex vivo analysis may be used as an additional diagnostic tool for quick examination of cancer and immune cells in whole tumor samples and to avoid false negatives in histological assays.

AB - NSCLC is a very aggressive solid tumor, with a poor prognosis due to post-surgical recurrence. Analysis of the specific tumor and immune signatures of NSCLC samples is a critical step in prognostic evaluation and management decisions for patients after surgery. Routine histological assays have some limitations. Therefore, new diagnostic tools with the capability to quickly recognize NSCLC subtypes and correctly identify various markers are needed. We developed a technique for ex vivo isolation of cancer and immune cells from surgical tumor and lung tissue samples of patients with NSCLC (adenocarcinomas and squamous cell carcinomas) and their examination on ex vivo cell preparations and, parallelly, on histological sections after Romanovsky–Giemsa and immunofluorescent/immunochemical staining for cancer-specific and immune-related markers. As a result, PD-L1 expression was detected for some patients only by ex vivo analysis. Immune cell profiling in the tumor microenvironment revealed significant differences in the immunological landscapes between the patients’ tumors, with smokers’ macrophages with simultaneous expression of pro- and anti-inflammatory cytokines, neutrophils, and eosinophils being the dominant populations. The proposed ex vivo analysis may be used as an additional diagnostic tool for quick examination of cancer and immune cells in whole tumor samples and to avoid false negatives in histological assays.

KW - PD-L1

KW - adenocarcinoma

KW - biomarkers

KW - eosinophils

KW - lung cancer

KW - macrophages

KW - squamous cell carcinoma

KW - tobacco smoking

KW - tumor microenvironment

UR - http://scopus.com/record/display.uri?eid=2-s2.0-85202484249&origin=inward&txGid=cdc2e1fabb2469c4a26377f0536f7922

UR - https://www.mendeley.com/catalogue/7d454de4-140c-3e11-ba54-b8f5da780d10/

U2 - 10.3390/cancers16162886

DO - 10.3390/cancers16162886

M3 - Article

C2 - 39199657

VL - 16

JO - Cancers

JF - Cancers

SN - 2072-6694

IS - 16

M1 - 2886

ER -