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Cyclophosphamide + tretinoin is a combination therapy that pairs cyclophosphamide, a nitrogen mustard alkylating agent, with tretinoin, a vitamin A derivative. Tretinoin pre-treatment has been shown to induce an inflammatory, interferon-associated tumor microenvironment with increased CD8+ T cell infiltration, potentially sensitizing tumors to subsequent cyclophosphamide chemotherapy. This combination has demonstrated significant improvement in survival and cure rates in some cancer models (specifically AB1-HA murine mesothelioma) in a CD4+ and CD8+ T cell dependent manner. However, the efficacy appears to be model-selective and has not been consistently replicated across different cancer cell lines.
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