Frontline pemetrexed and cisplatin based-chemotherapy combined with NRT promoted the antitumor in a mouse model of lung carcinoma

IF 4.8 2区医学 Q2 IMMUNOLOGY

International immunopharmacology Pub Date : 2025-02-09 DOI:10.1016/j.intimp.2025.114174

Xiaoqin Li , Hang Xu , Rujun Hong , Haitao Yang , Lihuan Xu , Guanying Zheng , Baosong Xie

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引用次数: 0

Abstract

The efficacy of neoantigen-reactive T cells (NRT) therapy in solid tumors, encompassing aspects such as infiltration, recognition, cytotoxicity, and enduring persistence, is notably influenced by the immunological microenvironment. This study endeavors to investigate whether the co-administration of pemetrexed and cisplatin augments the therapeutic efficacy of NRT therapy in lung cancer. Neoantigens were predicted using a comprehensive analysis of mutation data from Lewis lung carcinoma cells and mouse tail tissues. The immunogenicity of NRT cells was assessed through flow cytometry and IFN-γ ELISpot assays. A mouse model of NSCLC was used to investigate the anti-tumor effects of NRT combined with chemotherapy. The combination of NRT cells and chemotherapy significantly inhibited tumor growth in a mouse model, increased CD3+/CD137+ T cells to promote IFN-γ secretion from NRT cells, and up-regulated the levels of inflammatory cytokine proteins including IFN-γ, TNF, IL-6 and IL-10. Immunofluorescence analysis confirmed increased T-cell infiltration in tumor tissues without adverse effects on vital organs. In addition, transcriptome analyses indicated that the tumor microenvironment was altered to favor M1-like macrophages with an increased M1/M2 ratio, creating a pro-inflammatory environment. The integration of NRT with frontline chemotherapy for lung cancer could yield profoundly ideal therapeutic outcomes.

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来源期刊

International immunopharmacology 医学-免疫学

CiteScore

8.40

自引率

3.60%

发文量

935

审稿时长

53 days

期刊介绍： International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.