Tumor Antigens and Antigen-Presenting Capacity in Breast Cancer

Abstract

Aims: Cancer cells frequently express antigens capable of being recognized by the host immune system; however, any resultant immune response is often ineffective. This may be related in part to tumor-induced defects in antigen presentation. We screened for dendritic cell infiltration, tumor MHC II expression and associated lymphocytic reaction in the context of three established breast tumor antigens. Methods: Forty primary breast tumors were evaluated by immunohistochemical techniques for expression of her2/neu, p53, and MUC1 and MHC class II molecules. Twenty-five samples were further analyzed for p53 mutations by PCR-SSCP analysis and DNA sequencing. The phenotype of tumor-infiltrating inflammatory cells was evaluated using the following markers: CD1a, MHC Class II, CD3, CD45, and CD45RO. Results: Tumors with p53 mutations and overexpression, but not her2/neu or MUC1 overexpressing tumors, more frequently harbored marked CD1a+ dendritic cell infiltrates. An overall correlation between CD1a+ cell infiltrates and HLA class II expression on tumor cells (p = 0.0008) was also observed and these tumors had greater CD45RO+ lymphocytic infiltrates. Conclusions: In breast cancer, p53 mutations may present a more visible signal to the immune system and hence provide a better target for immunotherapy. Infiltrating CD1a positive cells are associated with a more dense tumor lymphocytic infiltrate and tumor cell expression of MHC II molecules.

Tumor HLA‐DR expression linked to early intrahepatic recurrence of hepatocellular carcinoma

“…Many studies have showed that MHC-class II antigens play a role in progression of malignant tumors via immunologic modification. [26][27][28][29][30][31] Our current results were consistent with their results. In this regard, our finding is not a new one.…”

Prognostic Value of Tumor-Infiltrating Dendritic Cells in Colorectal Cancer: Role of Maturation Status and Intratumoral Localization

“…A relationship between the amount of tumor-infiltrating CD1a-positive dendritic cells and expression of HLA class II on tumor cells has been observed in breast cancer (17). In the present study, we show the same correlation in colorectal cancer.…”

“…It is often being regarded as a marker for immature dendritic cells, which is down-regulated on maturation. However, different in vitro and in vivo studies have shown that CD1a can be present on both mature and immature dendritic cells (7,17). We used CD208 and CD1a to detect tumor-infiltrating dendritic cells.…”

<i>In vitro</i> analysis of T cell responses induced by breast tumor cell lysate pulsed with autologous dendritic cells

“…DCs originate from the bone marrow and reside in a resting or immature state in nonlymphoid tissues in which they efficiently capture and process antigens, Upon stimulation with bacterial products, inflammatory cytokines or CD40 ligation DCs undergo a maturation process that results in enhanced antigen presenting capacity and expression of MHC and costimulatory molecules and migration into secondary lymphoid organs in which they prime naive T cells [4][5][6]. The presence of DC at tumor site and regional lymph nodes pointed to a crucial role of these cells in antitumor immune responses [7,8]. Because of their unique capacity to stimulate resting T cells, DCs are the promising option for immunization protocols particularly for the induction of antitumor immunity to patients with malignant disease [9][10][11].…”