Immunogenic cell death-related biomarkers: Impact on the survival of breast cancer patients after adjuvant chemotherapy.

It is well established that the anticancer immune response determines the success of anthracycline-based adjuvant chemotherapy of breast cancer. This effect is in part due to the capacity of anthracyclines to induce immunogenic cell death (ICD), a cell death modality that is preceded by autophagy and followed by HMGB1 release. Recent data on 1,798 mammary carcinoma specimens indicate that patients harboring neoplastic cells that lack immunohistochemical signs of autophagy or that have lost HMGB1 expression have indeed a poor prognosis.

The presence of LC3B puncta and HMGB1 expression in malignant cells correlate with the immune infiltrate in breast cancer.

Several cell-intrinsic alterations have poor prognostic features in human breast cancer, as exemplified by the absence of MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3 β)-positive puncta in the cytoplasm (which indicates reduced autophagic flux) or the loss of nuclear HMGB1 expression by malignant cells. It is well established that breast cancer is under strong immunosurveillance, as reflected by the fact that scarce infiltration of the malignant lesion by CD8(+) cytotoxic T lymphocytes or comparatively dense infiltration by immunosuppressive cell types (such as FOXP3(+) regulatory T cells or CD68(+) tumor-associated macrophages), resulting in low CD8(+):FOXP3(+) or CD8(+):CD68(+) ratios, has a negative prognostic impact. Here, we reveal the surprising finding that cell-intrinsic features may influence the composition of the immune infiltrate in human breast cancer.

Combined evaluation of LC3B puncta and HMGB1 expression predicts residual risk of relapse after adjuvant chemotherapy in breast cancer.

In spite of adjuvant chemotherapy, a significant fraction of patients with localized breast cancer (BC) relapse after optimal treatment. We determined the occurrence of cytoplasmic MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3B)-positive puncta, as well as the presence of nuclear HMGB1 (high mobility group box 1) in cancer cells within surgical BC specimens by immunohistochemistry, first in a test cohort (152 patients) and then in a validation cohort of localized BC patients who all received adjuvant anthracycline-based chemotherapy (1646 patients). Cytoplasmic LC3B(+) puncta inversely correlated with the intensity of SQSTM1 staining, suggesting that a high percentage cells of LC3B(+) puncta reflects increased autophagic flux.

FOLFIRINOX bevacizumab is a promising therapy for chemorefractory metastatic colorectal cancer.

Purpose: Fluoropyrimidines, oxaliplatin, irinotecan and targeted therapies represent the standard treatment of metastatic colorectal cancer. After failure of all these treatments, few options are available. In such chemorefractory patients the effect of triplet chemotherapy with bevacizumab (FOLFIRINOX bevacizumab) has never been investigated.

FOXP3 expression in cancer cells and anthracyclines efficacy in patients with primary breast cancer treated with adjuvant chemotherapy in the phase III UNICANCER-PACS 01 trial.

Background: Predictive markers of response to chemotherapy are lacking in breast cancer patients. Forkhead Box Protein 3 (FOXP3) is an anti-oncogene whose absence in cancer cells could confer resistance to DNA damaging agent. So we made the hypothesis that FOXP3 expression predicts the response to anthracyclines in breast cancer patients and that adjuvant chemotherapy adding taxanes to anthracyclines confers an overall survival (OS) benefit over anthracyclines alone, in patients with FOXP3-negative tumors.

Role of myeloid-derived suppressor cells in tumor immunotherapy.

Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells that infiltrate human and experimental tumors and strongly inhibit anticancer immune response directly or by inducing regulatory T-lymphocyte activity. Consequently, MDSCs are important actors of cancer-induced immune tolerance and a major obstacle to efficiency of cancer immunotherapy. Several means of preventing MDSCs accumulation or inhibiting their immunosuppressive effect were recently discovered in cancer-bearing hosts, contributing to restoring antitumor immunity and consequently to control of tumor growth.