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]