Expression of the MHC class II in triple-negative breast cancer is associated with tumor-infiltrating lymphocytes and interferon signaling

Abstract

Tumor-infiltrating lymphocytes (TILs) have been known for their strong prognostic and predictive significance in triple-negative breast cancer (TNBC). Several mechanisms for TIL influx in TNBC have been elucidated. Major histocompatibility complex class II (MHC-II) is an essential component of the adaptive immune system and is generally restricted to the surface of antigen-presenting cells. However, it has been reported that interferon-gamma signaling may induce MHC-II in almost all cell types, including those derived from cancer. We aimed to examine the relationship between MHC-II expression in tumor cells and the amount of TILs in 681 patients with TNBC. Further, the prognostic significance of MHC-II and the association of MHC-II with a couple of molecules involved in the interferon signaling pathway were investigated using immunohistochemical staining. Higher MHC-II expression in tumor cells was associated with the absence of lymphovascular invasion (p = 0.042); larger amounts of TILs (p < 0.001); frequent formations of tertiary lymphoid structures (p < 0.001); higher expression of myxovirus resistance gene A, one of the main mediators of the interferon signaling pathway (p < 0.001); and higher expression of double-stranded RNA-activated protein kinase, which can be induced by interferons (p = 0.008). Moreover, tumors that showed high MHC class I expression and any positivity for MHC-II had larger amounts of CD4- and CD8-positive T lymphocytes (p < 0.001). Positive MHC-II expression in tumor cells was associated with better disease-free survival in patients who had lymph node metastasis (p = 0.009). In conclusion, MHC-II expression in tumor cells was closely associated with an increase in TIL number and interferon signaling in TNBC. Further studies are warranted to improve our understanding regarding TIL influx, as well as patients’ responses to immunotherapy.

Bovine herpesvirus 4-based vector delivering the full length xCT DNA efficiently protects mice from mammary cancer metastases by targeting cancer stem cells

“…This is noteworthy because T lymphocyte infiltration is associated with good prognosis in breast cancer patients, while the activation of IFN-γ-producing T helper 1 and CD8 + T cells is important for anti-cancer response. 46 The restimulation of splenocytes from BoHV-4-mxCT-vaccinated mice with 4T1 cells also increased the percentage of CD107 + T cells. Nevertheless, only a very slight increase in the ability of splenocytes to kill 4T1 cells in vitro was detected when compared with splenocytes from BoHV-4-A29 control mice.…”

A Multigene Assay Determines Risk of Recurrence in Patients with Triple-Negative Breast Cancer

“…9), which are known to be associated with good prognosis in patients with TNBC (10)(11)(12)(13)(14). An independent research team performed IHC on 681 TNBC patient tumors and confirmed that high expression of MHCII in tumor cells was associated with large amounts of tumor-infiltrating CD4-and CD8-positive T cells, and longer DFS (15). Mouse studies have shown that MHCII expression on tumor cells triggers T-cell recruitment and inhibits tumor progression (16)(17)(18)(19)(20)(21)(22)(23).…”

PIK3CA inKrasG12D/Trp53R172HTumor Cells Promotes Immune Evasion by Limiting Infiltration of T Cells in a Model of Pancreatic Cancer

“…Suppression of cell surface MHC I is a well-documented mechanism used by some tumors to evade the immune system [8]. Conversely, high MHC I expression in triple negative breast tumors is correlated with increased tumor-infiltrating lymphocytes and better prognosis in patients [40]. One important phenotype caused by Pik3ca loss in KPC cells is upregulation of MHC I on the cell surface.…”