Br J Cancer: Bovine white blood cell extract ICRP induces the occurrence of immunogenic cell death in breast cancer cells and builds long-term anti-tumor memory

Breast cancer (BC) is the most commonly diagnosed cancer and one of the main causes of death in women.
factors leading to death include distant metastasis of tumors and the ability to relapse up to 20 years after diagnosis, which are associated with lower immunogenicity of cancer cells.
cancer cells release the associated immunosuppressants and block the cancer's immune cycle.
, however, recent theories suggest that cancer cells can produce immunogenicity through appropriate immune response stimulation.
, immunogenic cell death (ICD) is a promising treatment strategy for converting cancer cells into their own vaccines to overcome disease recurrence.
ICRP (IMMUNEPOTENT CRP) is a dialysis white blood cell extract (DLE) extracted from ruptured spleen tissue in cattle, which acts as an immunomodulator and is cytotoxic to a variety of cancer cells.
, the study focused on assessing whether ICRP induces ICD in BC cells.
ICRP induced loss of mitochondrial membranes, autophagy formation, and the occurrence of ROS-dependent cell death researchers analyzed the main biogenic characteristics of ICD in MCF-7, MDA-MB-231, and 4T1 cells by evaluating the immunogenicity of ICRP-induced cell death.
's ability to induce DC maturation by evaluating ICRP-KCC cells (killed cancer cells KCC obtained from 4T1 cells treated with ICRP), as well as T-cell initiation and T-cell-mediated cytotoxicity.
, tumor establishment and anti-tumor immune memory were evaluated after vaccination of ICRP-KCC in the BALB/c mouse model.
results show that in BC cells, ICRP can induce caspase-dependent, ROS-dependent cell death responses, autophagy formation, phosphatization of eIF2 alpha, partner protein exposure, CD47 deficiency, and release of ATP and HMBG1.
addition, ICRP-KCC promotes DC maturation, triggering cytotoxicity of cancer cells initiated by T cells.
further studies showing that preventive vaccination of ICRP-KCC can prevent tumor formation in BALB/c mouse models and induce long-term anti-tumor memory, including the maturation of DC in the lymph nodes, the increase of CD8-T cells in the lymph nodes, the area of exosome blood and tumors, and the specific cells of lysotoxic tumors.
in general, the study results reveal that ICRP in BC cells can induce the occurrence of ICD, which can prevent tumor formation and cause long-term anti-tumor memory.