Clin Oncol | Volume 7, Issue 1 | Research Article | Open Access
Zhul Y1, Meng M2, Hou Z2, Wang W2, Li L2, Guan A1, Wang R1, Tang W2, Yang F3, Zhao Y2, Gao H2, Xie H1, Li R1* and Tan J1*
1Department of General Surgery, Yan'an Hospital Affiliated to Kunming Medical University, Kunming, China
2Key Laboratory of Tumor Immunological Prevention and Treatment in Yunnan Province, Yan’an Hospital Affiliated to Kunming Medical University, Kunming, China
3Department of Pathology, Yan’an Hospital Affiliated to Kunming Medical University, Kunming, China
Background: Expansion and activation of Cytotoxic T Lymphocytes (CTLs) in vitro represents a promising immunotherapeutic strategy, and CTLs can be primed by Dendritic Cells (DCs) loaded with Tumor-Associated Antigens (TAAs) transformed by recombinant Adeno-Associated Virus (rAAV). This study aimed to explore the impact of rAAV-DC-induced CTLs on prognosis of CRC and to explore factors associated with prognosis.
Methods: This prospective observational study included patients operated for resectable CRC at Yan’an Hospital Affiliated to Kunming Medical University between 2016 and 2019. The primary outcome was Progression-Free Survival (PFS), secondary outcomes were Overall Survival (OS) and adverse events. Totally 49 cases were included, with 29 and 20 administered rAAV-DC-induced CTL and chemotherapy, respectively. OS (P=0.0596) and PFS (P=0.0788) were comparable between two groups.
Results: After 37 to 69 months of follow-up (median, 54 months), mild fever occurred in 2 (6.9%) patients administered CTL infusion. All the chemotherapy group experienced mild-to-moderate adverse effects, including vasculitis (n=20, 100%), vomiting (n=5, 25%), nausea (n=17, 85%) and fatigue (n=17, 85%).
Conclusion: Lymphatic metastasis (Hazard Ratio [HR]=4.498, 95% Confidence Interval [CI]: 1.290-15.676; P=0.018) and lower HLA-Ⅰ expression (HR=0.294, 95% CI: 0.089-0.965; P=0.044) were associated with poor OS in the CTL group. CTLs induced by rAAV-DCs might achieve comparable effectiveness in CRC patients compare to chemotherapy, cases with high tumor-associated HLA-Ⅰ expression and no lymphatic metastasis were more likely to benefit from CTLs.
Colorectal neoplasm; Adoptive immunotherapy; T-Lymphocyte; Histocompatibility Antigens class 1; Lymphatic metastasis
Zhul Y, Meng M, Hou Z, Wang W, Li L, Guan A, et al. Impact of Cytotoxic T Lymphocytes Immunotherapy on Prognosis of Colorectal Cancer Patients. Clin Oncol. 2022;7:1969..