Effect of curcumin on anti-tumor immune cell profiles in colorectal cancer patients receiving cytotoxic chemotherapy.

145 Background: The interaction between cancer cells and the immune system critically influences tumor progression and response to therapy. Tumor-driven immune suppression—characterized by impaired antigen presentation, dysfunctional effector lymphocytes, and expansion of immunosuppressive cell populations—enables immune evasion and limits the effectiveness of immunotherapies. Curcumin, a natural polyphenol derived from Curcuma longa , is well known for its anti-inflammatory and anticancer properties and has recently emerged as a modulator of cancer immunity. Growing evidence suggests that curcumin regulates both innate and adaptive immune responses in the tumor microenvironment by targeting key inflammatory and oncogenic signaling pathways, thereby restoring antitumor immune surveillance and enhancing responsiveness to immune-based therapies. Methods: To evaluate the immunoregulatory effects of curcumin, a study was conducted in patients with stage IV colorectal cancer receiving chemotherapy. Peripheral blood samples were collected at baseline before curcumin administration, at 4 and 12 weeks during treatment, and again at 16 weeks after curcumin discontinuation. Immune cell populations were analyzed by flow cytometry using antibodies against CD3/CD4, CD3/CD8, IFN-γ/CD4, IL-5/CD4, IL-17A/CD4, IFN-γ/CD8, Foxp3, and natural killer (NK) cell markers. Results: Curcumin treatment significantly reshaped the immune profile. It reduced immunosuppressive regulatory T cells, myeloid-derived suppressor cells, and M2-polarized tumor-associated macrophages, while enhancing the abundance and activation of cytotoxic immune cells. Specifically, CD4⁺ T cells increased from 24% to 40%, CD8⁺ T cells from 17% to 24%, and cytotoxic T lymphocytes from 35% to 50%. In contrast, regulatory T cells decreased from 14% to 8%, and NK cells showed a marked expansion from 12% to 38%. These cellular changes were accompanied by increased production of effector molecules such as interferon-γ and granzyme B, along with a reduction in pro-tumorigenic inflammatory mediators. Conclusions: Overall, these findings demonstrate that curcumin effectively reprograms the tumor immune microenvironment toward an antitumor state by alleviating immune suppression and enhancing effector immune function. Its ability to augment immune-based cancer therapies supports curcumin as a rational and mechanistically grounded adjuvant in cancer immunotherapy, warranting further optimization and clinical evaluation.