A Study on Tumor-Infiltrating Lymphocytes in Different Subtypes of Breast Cancer

Dimitrova, Polina; Popovska, S; Ivanov, Ivan N.

doi:10.2478/jbcr-2021-0008

Cited by 2 publications

(2 citation statements)

References 33 publications

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“…Previous study by Rathore et al 19 showed that high stromal CD8 + count ( P <0.001) in the infiltrating ductal carcinoma of the breast had a high survival rate. A study by Dimitrova et al 20 showed high counts of CD8 + TILs in Her-2-positive and TNBC subtypes compared with the Luminal subtypes. Similarly, Oshi et al 21 also found high infiltration of CD4 + /CD8 + cells in TNBC and association with better survival.…”

Section: Discussionmentioning

confidence: 98%

Heterogeneity of the Tumor Microenvironment Across Molecular Subtypes of Breast Cancer

Kashyap,

Bal,

Irinike

et al. 2023

Applied Immunohistochemistry &Amp; Molecular Morphology

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Breast cancer is a heterogenous disease at the molecular level thus, it can be hypothesized that different molecular subtypes differ in their tumor microenvironment (TME) also. Understanding the TME heterogeneity may provide new prognostic biomarkers and new targets for cancer therapy. For deciphering heterogeneity in the TME, immunohistochemistry for immune markers (CD3, CD4, CD8, CD68, CD163, and programmed death-ligand 1), Cancer-associated fibroblast markers [anti-fibroblast activating protein α (FAP-α), platelet-derived growth factor receptor α (PDGFR-α), S100A4, Neuron-glial antigen 2, and Caveolin-1], and angiogenesis (CD31) was performed on tissue microarrays of different molecular subtypes of breast cancer. High CD3 + T cells were noted in the Luminal B subtype (P = 0.002) of which the majority were CD8 + cytotoxic T cells. Programmed death-ligand 1 expression in immune cells was highest in the human epidermal growth factor receptor 2 (Her-2)-positive and Luminal B subtypes compared with the triple-negative breast cancer (TNBC) subtype (P = 0.003). Her-2 subtype is rich in M2 tumor-associated macrophages (P = 0.000) compared with TNBC and Luminal B subtypes. M2 immune microenvironment correlated with high tumor grade and high Ki-67. Her-2 and TNBC subtypes are rich in extracellular matrix remodeling (FAP-α, P = 0.003), angiogenesis-promoting (PDGFR-α; P = 0.000) and invasion markers (Neuron-glial antigen 2, P = 0.000; S100A4, P = 0.07) compared with Luminal subtypes. Mean Microvessel density showed an increasing trend: Luminal A > Luminal B > Her-2 positive > TNBC; however, this difference was not statistically significant. The cancer-associated fibroblasts (FAP-α, PDGFR-α, and Neuron-glial antigen 2) showed a positive correlation with lymph node metastasis in specific subtypes. Immune cells, tumor-associated macrophage, and cancer-associated fibroblast-related stromal markers showed higher expression in Luminal B, Her-2 positive, and TNBC respectively. This differential expression of different components of TME indicates heterogeneity of the TME across molecular subtypes of breast cancer.

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Section: Discussionmentioning

confidence: 98%

Heterogeneity of the Tumor Microenvironment Across Molecular Subtypes of Breast Cancer

Kashyap,

Bal,

Irinike

et al. 2023

Applied Immunohistochemistry &Amp; Molecular Morphology

View full text Add to dashboard Cite

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“…The scoring of positive IHC-stained cells (colored brownish-with membrane and/or cytoplasmic expression for Tc; cytoplasmic for TAM), was performed independently by two pathologists who were not aware of the clinicopathological data of the studied cases. Similar to another study of ours [13], immunophenotyped lymphocytes (separately intratumoral and stromal) were counted (computer-assisted) and semiquantitatively graded. The average value of the results of the investigated cases with CC was taken as the cut-off.…”

Section: Immunohistochemical Examinationmentioning

confidence: 99%

Infiltration by Intratumor and Stromal CD8 and CD68 in Cervical Cancer

et al. 2023

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Background and Objectives: The tumor microenvironment (TME) plays a major role in neoplastic development. Various types of cells can be found in the TME. These cells can be classified into two groups, immunosuppressive and immunostimulatory types, depending on the function they perform in the antitumor immune response (IR). By interacting both with each other and with tumor cells, different immune mechanisms are activated or inhibited, which can suppress or promote the development and progression of cervical cancer (CC). Our aim was to investigate some of the main components of the cellular immune response in TME—tumor-infiltrating cytotoxic T cells (Tc, CD8+) and tumor-associated macrophages (TAMs, CD68+)—in patients with CC. Materials and Methods: We analyzed 72 paraffin-embedded tumor tissues of patients diagnosed and treated at Medical University Pleven, Bulgaria. Patients were classified according to the 2018 FIGO (International Federation of Gynaecology and Obstetrics) classification. From each patient, we selected one histological slide with hematoxylin eosin staining. In a microscopic evaluation, CD8+ T lymphocytes and CD68+-positive macrophages were counted in the tumor and stroma of five randomly selected fields at ×40 magnification (HPF). We analyzed the relationship between intratumoral and stromal CD8 and CD68 expression and FIGO stage and N status. Results: There was no significant association between the expression levels of intratumoral and stromal CD68+ cells in the different FIGO stages and according to the lymph nodes’ involvement. For CD8+ cells, the association of stromal infiltration was also not found, but T intratumor infiltration was associated with a higher FIGO stage, despite the fact that the results did not reach significance (p = 0.063, Fisher test). Intratumoral CD8+ cells were significantly associated with positive N status, (p = 0.035). Discussion: The separation of tumor-infiltrating cytotoxic T cells and tumor-associated macrophages into intratumoral and stromal is inconsequential. In our study, the level of infiltration of CD68+ cells in tumors and stromata was not significantly associated with tumor progression or lymph node involvement. The results were different for CD8+ cells, in which levels of infiltration were associated with lymph nodes’ statuses. Conclusions: The separate evaluation of CD68+ immune cells in the TME as intratumoral and stromal is not beneficial for defining prognoses, since the presence of these cells is not associated with the patient’s stage. In our study, the presence of CD8+ cells was significantly associated with lymph node metastases. The prognostic value of the obtained results can be enriched with an additional study of the lymphocyte phenotype, including B and other subtypes of T lymphocytes, NK cells, as well as molecules involved in the immune response, such as HLA subtypes.

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A Study on Tumor-Infiltrating Lymphocytes in Different Subtypes of Breast Cancer

Cited by 2 publications

References 33 publications

Heterogeneity of the Tumor Microenvironment Across Molecular Subtypes of Breast Cancer

Heterogeneity of the Tumor Microenvironment Across Molecular Subtypes of Breast Cancer

Infiltration by Intratumor and Stromal CD8 and CD68 in Cervical Cancer

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