Anti-cancer immune response mechanisms in neoadjuvant and targeted therapy

Abstract

Several studies suggest that the progression of malignant tumors as well as the response to chemotherapy and targeted therapy is critically dependent on the immunological parameters that are derived from the host immune system as well as a modulation of the immune system by therapeutic antibodies. It has been shown for many tumor types that the presence of a lymphocytic infiltrate in different types of cancers is a positive factor for clinical outcome and that the response to neoadjuvant chemotherapy is increased in a tumor with a prominent pretherapeutic infiltrate. Furthermore, new targeted therapies in breast cancer, such as trastuzumab, as well as in hematological malignancies, such as rituximab and alemtuzumab, have been shown to interact with immunological pathways, and this interaction is critical for response and clinical outcome. In neoplasms of lymphoid and hematopoietic tissues, targeted therapies not only reduce toxic effects on normal tissues but also lead to modulations of the immune system depending on the target molecule, its physiological function and cellular distribution. This review gives an overview on clinical data on response to classical chemotherapy as well as molecular targeted therapy and its interaction with the immune system.

Molecular Pathways: Involvement of Immune Pathways in the Therapeutic Response and Outcome in Breast Cancer

“…2). Interestingly, some biomarker studies corroborated these findings by showing that administration of trastuzumab induced attraction of macrophages and natural killer (NK) cells, that is, cells potentially involved in antibody-dependent cell-mediated cytotoxicity (ADCC), at the tumor site (3,4). NK cells are involved in the destruction of target cells through nonspecific mechanisms.…”

“…Overall, consistent studies report that immune activation at baseline, assessed by pathology or gene expression array, is associated with a higher likelihood of pathologic complete response after neoadjuvant chemotherapy (3). In all reports, this parameter added value to the current clinical and pathologic characteristics.…”

“…NK cells are involved in the destruction of target cells through nonspecific mechanisms. Several preclinical and biomarker data suggest that ADCC subsequently leads to the activation and expansion of tumor-specific cytotoxic T lymphocytes (3). These latter cells specifically recognize and kill cells that present a specific antigen (adaptive immune response; Fig.…”

Crosstalk between p38 and Smad3 through TGF-β1 in JEG-3 choriocarcinoma cells

“…The abnormal tissue of the mole can continue to grow even after it is removed. Although choriocarcinoma is a rare human malignancy which is curable, it is a potentially fatal disease (29). At present, availability of different diagnostic aids has turned the prognosis highly favorable (1), however, many patients still cannot get effective medical treatment.…”

How can grafted breast cancer models be optimized?

“…The immune system plays a key role in cancer development, eradication and progression. 49 In addition, some chemotherapies also influence the immune response. Administration of taxanes to women who were surgically treated for regional breast cancer was associated with higher levels of T-cell activation and NK cell activity when compared with a group of women not receiving taxanes.…”