Tumor Temporal Proteome Profiling Reveals the Immunological Triple Offensive Induced by Synthetic Anti-Cancer Salmonella

Abstract

The engineered “obligate” anaerobic Salmonella typhimurium strain YB1 shows a prominent ability to repress tumor growth and metastasis, which has great potential as a novel cancer immunotherapy. However, the antitumor mechanism of YB1 remains unelucidated. To resolve the proteome dynamics induced by the engineered bacteria, we applied tumor temporal proteome profiling on murine bladder tumors after intravenous injection of either YB1 or PBS as a negative control. Our data suggests that during the two weeks treatment of YB1 injections, the cured tumors experienced three distinct phases of the immune response. Two days after injection, the innate immune response was activated, particularly the complement and blood coagulation pathways. In the meantime, the phagocytosis was initiated. The professional phagocytes such as macrophages and neutrophils were recruited, especially the infiltration of iNOS+ and CD68+ cells was enhanced. Seven days after injection, substantial amount of T cells was observed at the invasion margin of the tumor. As a result, the tumor shrunk significantly. Overall, the temporal proteome profiling can systematically reveal the YB1 induced immune responses in tumor, showing great promise for elucidating the mechanism of bacteria-mediated cancer immunotherapy.

Bacterial‐Mediated Tumor Therapy: Old Treatment in a New Context

“…PC‐3 prostate cancer, [ 12 , 110 ] breast tumor, [ 109 , 111 ] HCC, [ 112 ] colon carcinomas, [ 109 , 111 , 112 , 113 ] CT26 colon cancer, [ 114 ] MC38 colon cancer, [ 115 ] schwannoma, [ 116 ] bladder cancer, [ 92 , 117 ] PDAC, [ 12 , 118 ] fibrosarcoma [ 119 ]…”

Salmonellacancer therapy metabolically disrupts tumours at the collateral cost of T cell immunity

“…It is widely reported that STm induces a cascade of immune changes within the tumour microenvironment—such as widespread immune cell influx, pro-inflammatory cytokine production, dendritic cell (DC) maturation and natural killer (NK) cell activation—that is believed to support immune tumour-clearance (Yang et al, 2021). Indeed, monocyte depletion (Johnson et al, 2021), NK cell depletion (Lin et al, 2021), or MyD88 deletion (Zheng et al, 2017) can wholly abrogate therapeutic success in vivo , underscoring the necessity of an innate-like response in this therapy.…”

Integration of CoAl-Layered Double Hydroxides on Commensal Bacteria to Enable Targeted Tumor Inhibition and Immunotherapy

“…Recently, some bacteria-based biohybrid systems show potential in synergistic cancer therapy. − Anaerobic or facultative anaerobic characteristics enable bacteria to possess hypoxia tropism for active tumor targeting. , In addition, the immunogenicity of bacteria facilitates it with immune activity. ,, Propionibacterium acnes (PA), as an anaerobic bacterium with oxygen tolerance, is a commensal organism in human skin . The hypoxic TME is preferential for PA to proliferate and metabolize.…”

“…13,14 In addition, the immunogenicity of bacteria facilitates it with immune activity. 13,15,16 Propionibacterium acnes (PA), as an anaerobic bacterium with oxygen tolerance, is a commensal organism in human skin. 17 The hypoxic TME is preferential for PA to proliferate and metabolize.…”

“…10−12 Anaerobic or facultative anaerobic characteristics enable bacteria to possess hypoxia tropism for active tumor targeting. 13,14 In addition, the immunogenicity of bacteria facilitates it with immune activity. 13,15,16 Propionibacterium acnes (PA), as an anaerobic bacterium with oxygen tolerance, is a commensal organism in human skin.…”