Increased expression of musashi 1 on breast cancer cells has implication to understand dormancy and survival in bone marrow.

Breast cancer (BC) stem cells (CSCs) resist treatment and can exist as dormant cells in tissues such as the bone marrow (BM). Years before clinical diagnosis, BC cells (BCCs) could migrate from the primary site where the BM niche cells facilitate dedifferentiation into CSCs. Additionally, dedifferentiation could occur by cell autonomous methods. Here we studied the role of Msi 1, a RNA-binding protein, Musashi I (Msi 1). We also analyzed its relationship with the T-cell inhibitory molecule programmed death-ligand 1 (PD-L1) in CSCs. PD-L1 is an immune checkpoint that is a target in immune therapy for cancers. Msi 1 can support BCC growth through stabilization of oncogenic transcripts and modulation of stem cell-related gene expression. We reported on a role for Msi 1 to maintain CSCs. This seemed to occur by the differentiation of CSCs to more matured BCCs. This correlated with increased transition from cycling quiescence and reduced expression of stem cell-linked genes. CSCs co-expressed Msi 1 and PD-L1. Msi 1 knockdown led to a significant decrease in CSCs with undetectable PD-L1. This study has implications for Msi 1 as a therapeutic target, in combination with immune checkpoint inhibitor. Such treatment could also prevent dedifferentiation of breast cancer to CSCs, and to reverse tumor dormancy. The proposed combined treatment might be appropriate for other solid tumors.

Harnessing antitumor immunity: Employment of tumor recall antigens to optimize the inflammatory response to cancer.

The advent of immunotherapy for cancer has contributed to the era of personalized medicine for cancer. The various immunotherapy-based treatments that have been explored thus far include monoclonal antibody therapy, tumor vaccines, immune checkpoint blockade and adoptive T cell transfer, among others. The groundwork for all these immunotherapeutic modalities rests within the tumor microenvironment, specifically the immune factors that influence the tumor-drug interface. Prior to therapeutic design, the tumor microenvironmental interactions and the current barriers to successful treatment must first be understood. In the present review, it is proposed that cancer cell eradication within the tumor niche may be achieved by reprogramming of the immune microenvironment in favor of a pro-inflammatory antitumor profile at an early stage. This pro-inflammatory profile may, in turn, be influenced by tumor recall antigens, which function to stimulate the cell-mediated or humoral responses involved in antitumor immunity. These measures serve to counteract the immunotolerant state of the tumor microenvironment. Such measures are critical to therapeutic successes.

Progressive Multifocal Leukoencephalopathy with Negative JC Virus PCR following Treatment of Follicular Lymphoma: Implications for Biologics in the Era of Targeted Cancer Therapy.

Anticancer therapy predisposes patients to infections by the immunosuppression that results from treatment. Although 85% of patients with progressive multifocal leukoencephalopathy (PML) have concurrent HIV/AIDS, PML can also develop in patients after they receive chemotherapy for cancer. The case herein describes a 69-year-old man with history of follicular lymphoma who presented with progressive dysarthria and right-sided paralysis. He received rituximab one year prior to presentation. PET scan suggested no recurrence of lymphoma. Cerebrospinal fluid (CSF) analysis was negative and showed fewer than 500 copies/mL of JC virus. However, brain biopsy showed chromatin margination and viropathic change within oligodendrocytes, confirming PML. He was started on mirtazapine and mefloquine with some clinical improvement. To our knowledge, this is the first case of rituximab-associated PML in a patient with negative JC virus PCR from the CSF. Recognition of PML in the differential of oncology patients with CNS symptoms is an important consideration as we enter the era of targeted therapy and personalized cancer medicine involving biologics. Furthermore, screening of patients for presence of subclinical JC viremia prior to the use of biologics may be an important component of assessing patient candidacy for these agents.