Abstract
Combination of immunotherapy and chemotherapy has shown promise for cancer. Interleukin-7 (IL-7) can potentially enhance immune responses against tumor, while oxaliplatin (OXP), a platinum-based drug, can promote a favorable immune microenvironment and stimulate anticancer immune responses. We evaluated the anti-tumor activity of IL-7 combining OXP against a murine colon carcinoma in vitro and in vivo and studied the tumor immune microenvironment to investigate whether the combined treatment affects on the local immune cell populations. Utilizing lung and abdomen metastasis models by inoculation of CT26 mice colon cancer cells, we evaluated the anti-tumor efficacy of combining IL-7 and OXP in mice models. Tumor immune microenvironment was evaluated by flow cytometric analysis and immunohistochemical staining. Our study showed that the in vivo administration of IL-7 combined with OXP markedly inhibited the growth of tumors in lung and abdomen metastasis models of colon cancer. IL-7 alone had no effect on tumor growth in mice and IL-7 did not alter cell sensitivity to OXP in culture. The antitumor effect of combining IL-7 and OXP correlated with a marked increase in the number of tumor-infiltrating activated CD8+ T cells and a marked decrease in the number of regulatory T (Treg) cells in spleen. Our data suggest that OXP plus IL-7 treatment inhibits tumor cell growth by immunoregulation rather than direct cytotoxicity. Our findings justify further evaluation of combining IL-7 and chemotherapy as a novel experimental cancer therapy.
Highlights
Oxaliplatin (OXP), which is commonly used in colorectal cancer, has been recently found to increase the immunogenicity of cancer cells and induce immunogenic cell death [1]
We evaluated the antitumor activity of IL-7 combined with OXP against a murine colon carcinoma in vitro and in vivo and examined the tumor immune microenvironment to investigate whether this combined treatment affects local immune cell populations
To determine whether IL-7 directly affects the growth of CT26 cells or enhances their sensitivity to OXP in vitro, the effect of IL-7 alone and of IL-7 plus OXP on CT26 cells was determined in culture
Summary
Oxaliplatin (OXP), which is commonly used in colorectal cancer, has been recently found to increase the immunogenicity of cancer cells and induce immunogenic cell death [1]. It has been found that OXP can enhance the immune response against tumors by decreasing regulatory/suppressor cells: regulatory T (Treg) cells and myeloid-derived suppressor cells (MDSCs) and increasing the ratio of cytotoxic CD8+T lymphocytes (effector cells) versus immunosuppressive cell populations in the tumor microenviroment [2,3,4]. Interleukin-7 (IL-7) is one of the Interleukin-2 (IL-2)-related cytokines that share and signal through the c-chain to affect T cell proliferation,development and homeostasis[5,6,7,8]. IL7 represents a potential treatment to enhance T-cell reconstitution and vaccine efficacy as it has distinct actions on different subsets of T-cells[11]. It has been demonstrated that tumor cell lines transfected with the IL-7 gene reduced
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