Suppression of established hepatocarcinoma in adjuvant only immunotherapy: alum triggers anti-tumor CD8+ T cell response.

Bo Wang,Jing Fu,Xuanyi Wang,Hongyang Wang,Yan Shi,Yumei Wen,Bin Wang,Zhangmei Ma

doi:10.1038/srep17695

Abstract

Dendritic cell-based immunotherapy is a new weapon in our battle against malignancies in human. Recent trials in human and research work in model animals have shown various degrees of success, suggesting its great potential for clinical use. While protocols vary, a common scheme in this category of treatment involves activation of dendritic cells, with the purpose of increasing antigen presentation and cellular immunity. Therefore, proper use of immune adjuvant is a central subject of study. We report here an unexpected finding that injection of alum, the most widely used human adjuvant, into mice carrying H22 hepatocarcinoma resulted in a significant reduction of tumor growth with extended animal survival. This effect was associated with an increased specific CD8+ T cell activation and an inflammatory environment, yet with minimal overt side effects. Our finding suggests that use of adjuvant alone in certain established tumors can invoke protective host immune activation against the same target, which may be of value in our development of new cancer immunotherapies.

Highlights

Treating metastatic melanoma[11,12,13]
Since antigens from established tumors are constantly presented by DCs, leading to immune tolerance in the absence of DC activation, proper stimulation of DCs may in theory reverse the inhibition and invoke tumor immunity
In our attempts to observe alum as an adjuvant to boost anti-tumor response against a Balb/c hepatoma line H22 initially established from a lymphatic metastatic model[35], we immunized H22 tumor-bearing mice with various isogenic tumor cell lysates in combination with alum to detect any potential therapeutic effect

Summary

Introduction

Treating metastatic melanoma[11,12,13]. Blocking PD-1/PD-L1 signaling has shown great efficacy in treating papilloma virus-induced malignant lesions and a list of other solid tumors[3,14]. Additional negative regulations are often present, including tumor-associated macrophages and suppressive cytokines such as TGFβ 20–22 In this case, adjuvant becomes critically important in triggering activation of DCs23. We report here an unexpected finding that in Balb/c mice with an established H22 hepatocarcinoma, a protocol of repeated alum injections invoked a tumor-specific immune response that significantly inhibited tumor growth and mortality. This response was critically dependent on the adoptive immune system, CD8+ T cells, and to a lesser extent neutrophils. Since alum is a well-tolerated adjuvant, our outcomes implicate its potential use in tumor treatment

Methods

Results

Conclusion