Background
Lenvatinib is a novel multiple receptor tyrosine kinase inhibitor used for hepatocellular carcinoma (HCC) treatment. Although its main function is to suppress VEGFR and FGFR pathway, its immunomodulatory activity in HCC is not elucidated. Thus, this study aimed to investigate the immunomodulatory capability of lenvatinib in HCC.
Material and methods
Totally 47 patients with HCC were enrolled in this study, and the immune cells and serum cytokine profiles before initiation of treatment and after 1 and 3 months were measured. The immune checkpoint receptors on the immune cells were also evaluated. Kaplan–Meier survival estimate and log rank tests were used to assess the prognostic value.
Result
The frequency of T helper (Th) cells and T regulatory (Treg) cells reduced after lenvatinib treatment, while cytotoxic T lymphocyte (CTL) cells increased significantly. The cytokine profiles showed IL‐2, IL‐5, IFN‐γ increased; other cytokines including IL‐6, IL‐10, TNF‐ α and TNF‐ β decreased with lenvatinib therapy. Furthermore, the PD‐1 and TIM‐3 expressed on CTL had greatly decreased; the expression of TIM‐3 and CTLA‐4 was reduced on Treg cells as well. Besides, the new index CTL/Treg ratio was created, and low ratio was associated with the unfavorable outcome of HCC patients.
Conclusion
Our results confirmed that lenvatinib is capable of improving patients’ immune status, saving the effector cells from exhaustion status and inhibiting the number and function of immunosuppressive cells. The novel index CTL/Treg ratio qualifies as a predictor for the outcome of patients with lenvatinib therapy.
So far, ovarian cancer has still been the most lethal gynecological malignancy. The chemotherapy and targeted medication are the mainstay for the recurrent ovarian cancer treatment. About 70% of the advanced-stage cases will relapse. Ascites-derived organoid is a pre-clinical model for the precise prediction of the therapeutic effectiveness for the ovarian cancer: it can be used to assess the drug sensitivity, to guide individualized precise treatment, and to improve advanced stage as well as recurrent ovarian cancer patient’ survival and prognosis. Until now, there has been no report concerning the establishment of the organoid out of the patient’s ascites and the concurrent usage of drug sensitivity test to guide the individualized precise treatment for the ovarian cancer. Here, we report a case of recurrent ovarian cancer of a 59-year-old female patient whose CA125 at its peak increased to 4523.4 U/mL. Then, patient’s own ovarian cancer organoid was constructed from the ascites by the abdominocentesis; concurrently, medication sensitivity test was performed on the organoid to guide individualized precise treatment. After the treatment, CA125 decreased to 33.7 U/mL, and the patient’s condition relieved effectively. This is the first published case report using ascites-derived organoid and the drug sensitivity test thereof to guide the precise treatment of recurrent ovarian cancer.
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