Immune parameters associated with survival in metaplastic breast cancer

Abstract

Background: Metaplastic breast carcinoma (MBC) is a rare histological type of breast cancer, which commonly shows resistance to standard therapies and is associated with poor prognosis. The immune microenvironment in MBC and its significance has not been well established due to its low incurrence rate and complex components. We aimed to investigate the diversity of immune parameters including subsets of TILs and PDL1/PD1 expression in MBC, as well as its correlation with prognosis. Methods: A total of 60 patients diagnosed with MBC from January 2006 to December 2017 were included in our study. The percentage (%) and quantification (per mm 2) of TILs and presence of tertiary lymphoid structures (TLS) were evaluated by hematoxylin and eosin staining (HE). The quantification of CD4+, CD8+ TILs (per mm 2), and PD-1/PDL1 expression were evaluated through immunohistochemistry and analyzed in relation to clinicopathological characteristics. A ≥ 1% membranous or cytoplasmatic expression of PD1 and PDL1 was considered a positive expression. Results: We found squamous cell carcinoma MBC (33/60, 55%) exhibiting most TILs of all the MBC subtypes (p = 0.043). Thirty-three of 60 (50%) of the patients had coexisting invasive ductal carcinoma of no special type (IDC-NST), and the average percentage of TILs in MBC components was lower compared with NST components (p < 0.001). Thirty (50%) patients exhibited positive (≥ 1%) PDL1 expression in their tumor cells, while 36 (60%) had positive (≥ 1%) PDL1 expression in their TILs. Twenty-seven (45%) of all the patients had positive (≥ 1%) PD1 expression in their tumor cells and 33 (55%) had PD1-positive (≥ 1%) stromal TILs. More CD8+ TILs were associated with positive PDL1 expression of tumor cells as well as positive PD1 expression in stromal cells. Greater number of stromal TILS (> 300/mm 2 , 20%), CD4+ TILs (> 250/mm 2), and CD8+ TILs (> 70/mm 2) in MBC were found associated with longer disease-free survival. Positive expression of PDL1 in tumor cells (≥ 1%) and PD1 in stromal cells (≥ 1%) were also associated with longer survival. Conclusions: The immune characteristics differ in various subtypes as well as components of MBC. Immune parameters are key predictive factors of MBC and provide the clinical significance of applying immune checkpoint therapies in patients with MBC.

Sphingosine-1-Phosphate Catabolizing Enzymes Predict Better Prognosis in Triple-Negative Breast Cancer Patients and Correlates With Tumor-Infiltrating Immune Cells

“…Expression of S1PR4 is restricted to lymphoid and hematopoietic tissues, and it has been shown previously that S 1 PR4- deficient mice have reduced numbers of plasmacytoid DCs (pDCs), which has been partly attributed to defects in the differentiation of pDC progenitors into mature pDCs ( Dillmann et al, 2015 ). Infiltration of immune cells, including CD4+ and CD8+ T lymphocytes and DCs into tumors, is associated with better survival of patients with TNBC ( Chao et al, 2020 ). We demonstrated herein that the expression of SGPP1 , PLPP3, and S1P receptors, particularly S1PR4, positively correlates with tumor-infiltrating DCs in TNBC.…”

A Machine Learning Approach to Differentiate Two Specific Breast Cancer Subtypes Using Androgen Receptor Pathway Genes

“…Recent studies revealed that MBC has more tumor-infiltrating lymphocytes and showed higher PD-L1 expression in both tumor cells and stromal lymphocytes. 26 Thus, whether MBC has similarity with the immunomodulatory subtype still need to be elucidated. The more sophisticated classification of TNBC would enable us to have a better understanding of its molecular mechanism and promote the development of precision medicine.…”

Epithelial Mesenchymal Transition and Immune Response in Metaplastic Breast Carcinoma

“…Although there were methodological and result differences among the series, all of them demonstrated that a high percentage of MBC (30 to 70%) expressed PD-L1 in tumor cells. In addition, most studies also observed higher expression of PD-L1 [ 13 , 30 , 133 , 134 , 135 , 136 , 137 ] in MBC than in other types of TNBCs. [ 30 , 133 , 135 ].…”

“…Thus, in the study by Joneja et al [ 30 ], although total TILs were not enumerated, it was noted that TILs vary greatly within the MBC cohort by histologic examination. Chao et al [ 134 ] found sqCC MBC exhibiting most TILs of all the MBC subtypes. Similarly, Lien et al [ 138 ] reported that sqCC exhibited the highest positivity rate of TILs, while matrix-producing carcinoma had the lowest.…”

“…There is controversy regarding the association between TILS and longer disease-free survival in MBCs. Chao et al [ 134 ] and Chien et al [ 138 ] found a relationship between a greater number of TILS and longer disease-free survival, but Kalaw et al [ 135 ] found that TILs content did not significantly impact BC-specific survival in their MBC cohort. The latter authors observed that an increased amount of FOXP3 positive intra-tumoral TILs was associated with an adverse prognostic outcome [ 135 ].…”