Table 6.

Impact of intratumoural microbiota on cancer treatment

Favorable results
Intratumoural microbiota	Potential mechanisms	Results	Tumor type	Cells	Species	References
E.coli	Expression of cytosine deaminase gene of Escherichia coli in intratumoural attenuated Salmonella	Increased conversion of 5-fluorouracil	Squamous cell and oesophageal adenocarcinoma of the head and neck	Pilot Clinical Trial Organisation	human beings	[103]
HPV	Radiation increases levels of residual double-stranded DNA breaks and G2 blockade in HPV cells	High radiosensitivity of HPV + tumors	Squamous cell carcinoma of the head and neck	hsc4, cal33, sat, ut-5	human beings	[104]
EBV, Herpes virus	(1) Expression of higher levels of drug immune checkpoints (e.g., PD-L1)	Enhanced anti-PD-1/PD-L1 immune checkpoint blockade response in virus-associated cancers	EBV + gastric cancer, herpesvirus-associated Kaposi's sarcoma	Clinical trial tissue with primary human monocytes	human beings	[105]
HIV	(2) Molecular mimicry: recognition of autoantigens initially generated from heterologous antigens			Memory B cells	human beings	[106]
Salmonella, Listeria, etc	(3) Direct involvement of innate immunity and TLR-mediated host responses in the tumor microenvironment		Adenocarcinoma of the colon	MC-38	C57BL/6 and BALB/C thymus Nu-/Nu- mice	[107]
E.coli	(4) Enhanced acute IFN-g response by outer membrane vesicles derived from Escherichia coli		Adenocarcinoma of the colon	CT-26, MC-38	BALB/c and C57BL/6 mice	[108]
Kaposi's sarcoma-associated herpesvirus (KSHV)	(5) Increased expression of pro-inflammatory cytokines (IL-1a, IL1b and IL-6)		Herpesvirus-associated Kaposi's sarcoma	Human mononuclear cells	human beings	[105]
EBV	TCR directly identifies viruses in pericyte therapy	Viruses as targets for immunotherapy	EBV-associated lymphoproliferative disorders after transplantation	Clinical trials	human beings	[109]
Harmful results
Intratumoural microbiota	Potential mechanisms	Results	Tumor type	Cells	Species	References
Gamma Proteobacteria	Inactivation of the long subtype of cytidine deaminase (CCDL), an enzyme produced by Gamma Proteobacteria	Gemcitabine inactivated	Colorectal cancer	MC-26	BALB/c mice	[21]
F. nucleatum	Activation of the autophagic pathway through TLR4 and MYD88 immune signalling and miR18 and miR-4802	Resistance to apoptosis by oxaliplatin and fluorouracil	Colorectal cancer	HT-29 HCT116 and SW480	Naked BALB/c mice	[25]
E.coli	Reactivation of drugs by B-glucuronidase bacterial enzyme	Increased irinotecan-associated diarrhoea		Proximal colonic cells	BALB/c mice	[110]
	(1) Promotes tolerogenic immune microenvironment by activating specific Toll-like receptors in monocytes	Reduced efficacy of anti-PD-1 immune checkpoint blockade in pancreatic cancer	Ductal adenocarcinoma of the pancreas	KPC cells PAN02 cells	KC, KPC, OT-I, OT-II and C57BL/6WT rats	[111]
Salmonella	(2) Bacterial production of metabolites (e.g. SCFA) leading to reduced release of pro-inflammatory chemokines and cytokines			Human monocyte-derived dendritic cells	human beings	[112]
Campylobacter jejuni	(3) Bacterial toxins, such as lethal cell swelling toxin (CDT), limit lymphocyte expansion by blocking IL-2 production			70Z/3 and Jurkat3KB5.2 cells	human beings, mouse	[113]
F. nucleatum	(4) RecruIntratumoural bacteriaent of tumor-infiltrating myeloid immune cells by F. nucleatum		Colorectal cancer		Mice	[55]
F. nucleatum	(5) F. nucleatum induces alternative immune checkpoints, e.g. TIGIT		Melanoma	Human melanoma cell lines, NK cells, T cells and DCs	human beings	[114]