Immune checkpoint inhibitors for triple-negative breast cancer: From immunological mechanisms to clinical evidence.

Breast cancer is the most common cancer type in women worldwide. Triple-negative breast cancer (TNBC), which is characterized by the absence of estrogen receptor/progesterone receptor (ER/PR) and human epidermal growth factor receptor 2 (Her2) expressions, has a poorer prognosis compared with non-TNBC breast tumors. Until recently systemic treatment for TNBC was confined to chemotherapy owing to the lack of actionable targets. Immune checkpoint molecules are expressed on malignant cells or tumor-infiltrating immune cells and can inhibit anti-cancer immune responses. Immune checkpoint inhibitors (ICI), including anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), anti-programmed cell death protein 1 (PD-1), and anti-programmed cell death 1 ligand 1 (PD-L1), induce immune responses in different types of neoplasms. They have recently gained attention for their possible role in TNBC treatment. Several clinical trials have been conducted on the role of immune checkpoint blockade in different settings for TNBC treatment. Available evidence justifies the application of ICI and chemotherapy combination in the management of metastatic TNBC and early-stage TNBC in neoadjuvant setting. This study aims to provide information on the mechanisms of action of ICIs, review the efficacy results of clinical trials using ICIs for TNBC treatment, and assess the side effects of such drugs.

Attribution of Ghrelin to Cancer; Attempts to Unravel an Apparent Controversy.

Ghrelin is an endogenous peptide hormone mainly produced in the stomach. It has been known to regulate energy homeostasis, stimulate secretion of growth hormone, and mediate many other physiologic effects. Various effects attributed to ghrelin contribute to many aspects of cancer development and progression. Accordingly, a large body of evidence has emerged about the association of ghrelin with several types of cancer in scales of cell-line, animal, and human studies. However, existing data are controversial. This controversy occurs in two main domains: one is the controversial results in local effects of ghrelin on different types of human cancer cell-lines; the second is the apparent disagreement in the results of in-vitro and clinical studies that investigated ghrelin association to one type of cancer. These inconsistencies have hampered the indications to consider ghrelin as a potential tumor biomarker or therapeutic agent in cancer patients. Previous studies have reviewed different parts of current literature about the ghrelin-cancer relationship. Although they have highlighted these controversial results in various ways, no specific recommendations have been given to address it. In this study, we comprehensively reviewed in-vitro, in-vivo, and clinical studies and attempted to use the following approaches to unravel the inconsistencies detected: (a) to distinguish local and systemic effects of ghrelin in interpreting its summary clinical role in each cancer; (b) scrutinizing factors that regulate local effects of ghrelin and could justify different effects of ghrelin on different cancer cell-lines. These approaches could have notable implications for future in-vitro and clinical studies.

Roles of Myeloid-Derived Suppressor Cells in Cancer Metastasis: Immunosuppression and Beyond.

Metastasis is the direst face of cancer, and it is not a feature solely dependent on cancer cells; however, a complex interaction between cancer cells and host causes this process. Investigating the mechanisms of metastasis can lead to its control. Myeloid-derived suppressor cells (MDSCs) are key components of tumor microenvironment that favor cancer progression. These cells result from altered myelopoiesis in response to the presence of tumor. The most recognized function of MDSCs is suppressing anti-tumor immune responses. Strikingly, these cells are among important players in cancer dissemination and metastasis. They can exert their effect on metastatic process by affecting anti-cancer immunity, epithelial-mesenchymal transition, cancer stem cell formation, angiogenesis, establishing premetastatic niche, and supporting cancer cell survival and growth in metastatic sites. In this article, we review and discuss the mechanisms by which MDSCs contribute to cancer metastasis.