Changes in Immunological Status in Patients With Metastatic Colorectal Cancer Treated With First-line Chemoimmunotherapy

Abstract

Background/Aim: Chemoimmunotherapy is a promising treatment for various malignant diseases. In this study, we examined whether first-line chemoimmunotherapy using adoptive immune-cell therapy was effective for metastatic colorectal cancer (mCRC). Patients and Methods: The therapeutic efficacy and safety of the standard first-line chemoimmunotherapy with adoptive αβ T cell therapy and bevacizumab were assessed using thirty-two patients with mCRC in our hospital. Immunological status after this chemoimmunotherapy was also evaluated. Results: The response and disease control rates were 68.8% and 87.5%, respectively. Further, median progression-free and overall survival were 14.2 and 35.3 months. Immunotherapyassociated toxicity was minimal. Significant decrease in the change of monocyte number (p=0.006) and increase in the change of rate of lymphocyte-to-monocyte ratio (p=0.039) were seen in the complete response group. Conclusion: Firstline chemoimmunotherapy with adoptive αβ T cell therapy may be useful for mCRC.Colorectal cancer (CRC) is one of the major malignant diseases in Japan (1). Chemotherapy is one of the effective treatments for CRC, and various novel chemotherapeutic agents including oxaliplatin, irinotecan and targeted therapies have contributed to the improvement of the prognosis (2). However, the prognosis of metastatic CRC (mCRC) remains poor (3-5). Therefore, the development of a novel therapy overcoming mCRC is urgent.Recently, immunotherapy is considered as a promising therapeutic strategy for advanced cancers. In particular, blockade of T cell inhibitory checkpoint molecules can unleash anti-tumour T cell activity and lead to long-term clinical responses in patients with advanced malignant diseases including lung cancer, melanoma, and Hodgkin's disease (6-10). However, patients in mCRC rarely enjoy the benefits of the current immune checkpoint blockade regimens due to inherent tumour cell resistance or extrinsic factors restraining anti-tumour immunity (11). Therefore, establishment of further improved immunotherapy for mCRC is a pivotal challenge.Adoptive immune-cell therapy is a novel cancer immunotherapy characterized as the re-infusion of ex vivoactivated and expanded T cells, such as αβ T cells, γδ T cells and natural killer cells. It has been proposed that adoptive immune-cell therapy stimulates and restores anti-tumour immunity because it enables immune cells to recognize and terminate tumour cells (12). Additionally, this therapy has a limited toxicity profile as opposed to established chemotherapy and checkpoint blockade (13-15). Among them, ex vivoexpanded αβ T cells have been studied for their antitumor effects (16,17) and applied to treatment of some cancers including hepatocellular carcinoma (18) and lung cancer (19) in the clinical setting. Recently, chemoimmunotherapy, defined 4763