The cryo-thermal therapy-induced IL-6-rich acute pro-inflammatory response promoted DCs phenotypic maturation as the prerequisite to CD4⁺T cell differentiation

Abstract

In our previous studies, a novel tumour therapeutic modality of the cryo-thermal therapy has been developed leading to long-term survival in 4T1 murine mammary carcinoma model. The cryo-thermal therapy induced the strong acute inflammatory response and IL-6 was identified in an acute profile. In this study, we found that the cryo-thermal therapy triggered robust acute inflammatory response with high expression of IL-6 locally and systemically. The phenotypic maturation of dendritic cells (DCs) was induced by acute IL-6 following the treatment. The mature DCs promoted CD4 T cell differentiation. Moreover, the production of interferon γ (IFN γ) in the serum and CD4 T cells were both abrogated by IL-6 neutralisation following the treatment. Our findings revealed that the cryo-thermal therapy-induced acute IL-6 played an important role in initiating the cascading innate and adaptive anti-tumour immune responses, resulting in CD4 T cell differentiation. It would be interesting to investigate acute IL-6 as an early indicator in predicating tumour therapeutic effect.

Neoantigen-specific CD4+T-cell response is critical for the therapeutic efficacy of cryo-thermal therapy

“…29 Our previous studies demonstrated that the percentage of CD4 + and CD8 + T-cells was significantly increased after cryo-thermal therapy. [17][18][19] However, whether tumor antigen-specific CD4 + and CD8 + T-cells were induced by cryo-thermal therapy had not been addressed. MHC-Irestricted peptides of TRP2, tyrosinase and gp100, three known antigens of B16F10 melanoma 21 were used to estimate the frequency of antigen-specific CD8 + T-cells, and MHC-II-restricted peptides of B16-M30 and B16-M20, two neoantigens of B16F10 melanoma 21 were used to estimate the frequency of antigen-specific CD4 + T-cells.…”

Hyperthermia Targeting the Tumor Microenvironment Facilitates Immune Checkpoint Inhibitors

“…DC maturation induced by thermal therapy is a prerequisite for CD4 T cell differentiation ( 57 , 71 ). Besides fever-range hyperthermia (39–40°C) inhibits Th2 and Treg growth, induces spleen Th1 and Tc1 proliferation, and promotes Th1 cell-associated secretion of IL-2, IFN- γ and TNF-α in spleen ( 72 ).…”

“…Among cytokines and chemokines induced by thermal stress, IL-6 plays a pivotal role in the tumor immune microenvironment. Specifically, cryo-thermal therapy-induced IL-6-rich acute pro-inflammatory response promotes DC phenotypic maturation, CD4(+) T cell differentiation, and Th1 anti-tumor immunity ( 71 , 82 ). In addition, hyperthermia induces M1 macrophages to secrete CXCL10 and IL-6 to induce CD4 T cell differentiation into Th1 and CD4 CTL cells, and reduce MDSC aggregation ( 57 ).…”

Co‐ablation versus cryoablation for the treatment of stage III–IV non‐small cell lung cancer: A prospective, noninferiority, randomized, controlled trial (RCT)

“…Nowadays, current developments are focusing on cryoimmunology, 21,22 which might play an important role in the future treatment of cancer. Some studies have found that combined ablation could generate a more powerful antitumor immune response, 23,24 and cryoablation combined with immunotherapy may significantly enhance antitumor efficacy 25 . Therefore, the strategy of combining coablation and immune therapy may be the focus in our future study.…”