Cell reveals that the lack of such lymphocytes can protect cancer cells and resist tumor treatment

The interaction between mammals and microorganisms has a profound impact on cancer
.

According to reports, several chronic infections are directly related to the development of cancer.

Innate lymphocytes (ILC) are a kind of tissue-resident innate lymphocytes that have received wide attention recently
.

They play a key role in regulating the host-microbe interaction on the mucosal barrier surface of the mammalian body .

On August 17, 2021, the international academic journal "Cell" published an online study titled "Dysregulation of ILC3s unleashes progression and immunotherapy resistance in colon cancer" from Cornell University's Gregory F.
Sonnenberg group
.

The study found that the imbalance of ILC3 promotes the progression of colon cancer and resistance to immunotherapy

DOI: 10.
1016/j.
cell.
2021.
07.
029

The researchers collected 72 patients with colorectal cancer and adjacent tissue specimens, and comprehensively analyzed their clinical and pathological data, and found that CD45+ cells in colorectal cancer significantly reduced ILC3s, and obtained the same results in spontaneous colon cancer mouse models.

.

Subsequently, the researchers sorted and purified ILC3s for RNA-seq and found that NKp46+ ILC3s decreased significantly, CCR6+ ILC3s increased significantly, and the plasticity to ILC1s or ex-ILC3s increased

ILC3 in tumors and non-malignant adjacent tissues of patients with colorectal cancer

Subsequently, the researchers conducted in-depth studies on the interaction between ILC3s and adaptive immunity in colorectal cancer, and observed that TH17 increased and TH1 cells decreased in tumors of patients and model mice
.

At the same time, its gut microbiota is significantly different from the control group, and is similar to the gut microbiota of IBD patients

MHCII+ ILC3s prevent the progression and invasion of experimental colorectal cancer

On the other hand, the researchers subcutaneously implanted the MC38 colon tumor cell line into littermate control mice and MHCIDILC3 mice, and applied PD-1 monoclonal antibody to the two groups of mice
.

In the control group, the tumor was strongly controlled, while the MHCIDILC3 mice showed significant drug resistance

MHCII+ ILC3s preserve type 1 immunity in tumors and prevent resistance to immunotherapy

Researchers hypothesized that the microbiota of patients with IBD does not promote type I immunity and will hinder immunotherapy
.

Compared with healthy people, colorectal biopsy of patients with active IBD has reduced ILC3s and increased T cell/ILC3 ratio

IBD patients contain microbiota that cause resistance to immunotherapy

Collectively, these data confirm the protective role of ILC3 in cancer and show that their inherent interference in CRC can lead to adaptive immune dysfunction, tumor progression, and resistance to immunotherapy
.

These findings are of great significance for the treatment of IBD patients and the application of immune checkpoint blockade therapy in gastrointestinal cancers.