Antineoplastic inhibitors may have a dual effect

Figure 1. Tissue transglutaminase (TG2) promotes peritoneal tumor growth in a mouse model of syngeneic ovarian cancer (OC) by preventing CD8 + T cell infiltration into ascites. (A, B) Ascites Volume of ascites (mean ± SEM, n = 23 per group, cumulative data from 4 independent experiments are shown) (A), and number of cells in ascites (mean ± SEM, Representative of one of two performed experiments in C57BL / 6 (TG2 + / +) and TG2 knockout (TG2-/-) female mice 6 weeks after intraperitoneal injection of ID8 cells, n = 5 per group Data from a typical experiment are shown) (B). Shown is the p-value for the t-test. (C) Images of TG2 + / + and TG2-/-intraperitoneal peritoneal metastases. Tumor implants are indicated by blue arrows. (D) Kaplan-Meier survival analysis of TG2 + / + (n = 12) and TG2-/-(n = 14) mice injected intraperitoneally with ID8 cells. The graph represents data from one of the two experiments performed. (E–H) Flow cytometric measurement of the percentage of immune cells in tumors with TG2 + / + and TG2-/- mice induced by intraperitoneal inoculation of ID8 cells. (E) CD8 + and CD4 + T cells in the spleen (TG2 + / +, n = 10; TG2-/-, n = 9; data from two experiments). (F) CD8 + and CD4 + T cells in abdominal ascites (TG2 + / +, n = 13; TG2-/-, n = 16; data from 4 experiments). (E, F) Program expressing CD8 + T cells in spleen (n = 7 per group; data from one representative experiment) and ascites (n = 9 per group; pooled data from three experiments) Cell death protein 1 (PD-1). Values ​​are mean ± SEM (* p)

TG2, an enzyme known to help cancer spread faster, also plays a role in the regulation of T cells, according to a study by Northwestern Medicine published in. Journal for ImmunoTherapy of Cancer..

Inhibiting TG2 in non-cancer cells also increases immune activity. this is, Cancer treatment, According to Daniela Matei, MD, Professor of Cancer Studies in Princess Wales, Head of Reproductive Sciences in Obstetrics and Gynecology Medicine, and Senior Author of the Study.

“If you create a drug that inhibits TG2, it can work in cancer and host cells,” said Matei, a professor of medicine in the Department of Hematology and Oncology.

Matei’s lab has been studying the effects of elevated TG2 expression in ovarian cancer for 10 years and has consistently found that TG2 increases the spread of ovarian cancer elsewhere in the body.However, what kind of effect does TG2 have? Normal cells It remained unknown.

In the current study, Matei and co-authors Bin Zhang, MD, Ph.D. Is a professor of medicine in the Department of Hematology Oncology and Microbiology-Immunology, studying the effects of knocking out the expression of the gene encoding TG2.With a mouse model Ovarian cancer..

Researchers have surprisingly found that loss of TG2 in healthy cells is associated with a stronger immune response. In the absence of TG2, STAT protein imbalances cause increased cytotoxic T cell activity and slow tumor progression.

“We believe that loss of TG2 causes this compensatory mechanism because TG2 is needed in the body,” Matei said.

Matei and co-workers are currently looking for strategies to block TG2 in cancer cells, but are currently designing inhibitors that also work in immune cells.

“Our current inhibitors are cancer cells Extracellular matrix, But other approaches can degrade the entire TG2 protein-it may help kill cancer cell, Altering anti-tumor immunity and slowing the progression of cancer. ”

Platinum chemotherapy can increase the resistance of ovarian cancer cells to treatment

For more information:
Livia Elena Sima et al, loss of host tissue transglutaminase, enhances antitumor T cell immunity by altering STAT1 / STAT3 phosphorylation in ovarian cancer. Journal for ImmunoTherapy of Cancer (2021). DOI: 10.1136 / jitc-2021-002682

Quote: Anti-cancer inhibitors have a dual effect (2021) obtained on October 22, 2021 from https: // May 22nd)

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Antineoplastic inhibitors may have a dual effect

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