Immune checkpoint inhibitors are the most widely utilized immunotherapies. They function by identifying and inhibiting the proteins that cancer cells employ to conceal from the immune system. Cancer cells that lack these proteins, on the other hand, employ a variety of hiding strategies.
Patients with these tumors do not respond to immune checkpoint inhibitors, thus researchers are looking for alternative strategies to develop immunotherapies with distinct targets. Researchers at Osaka University have discovered that tetracycline antibiotics aid the immune system in detecting cancer cells in a way that differs from conventional immunotherapies.
The study’s findings were published in the Journal for ImmunoTherapy of Cancer in an article titled “Tetracyclines enhance anti-tumor T cell immunity via the Zap70 signaling pathway.“
Tetracycline antibiotics have been used to treat infectious infections for a long time. Now, these ancient medications could pave the path for new immunotherapies for cancer patients who now have few therapy alternatives.
“Cancer immunotherapy including immune checkpoint inhibitors is only effective for a limited population of patients with cancer,” the study’s authors stated.
“Therefore, the development of innovative cancer immunotherapy is expected. Tetracyclines were shown in preliminary investigations to boost T-cell responses. Therefore, we studied the efficacy of tetracyclines on antitumor T-cell responses using human peripheral T cells, murine models, and the lung tumor tissues of patients with non-small cell lung cancer (NSCLC), with an emphasis on signaling pathways in T cells.”
The researchers looked at the tetracycline antibiotic minocycline in blood and tumor tissue from lung cancer patients.
“The cytotoxicity of peripheral and lung tumor-infiltrated human T cells against tumor cells was assessed by using bispecific T-cell engager (BiTE) technology (BiTE-assay system),” according to the study.
“The effects of tetracyclines on T lymphocytes in the peripheral blood of healthy donors and tumor tissues of patients with NSCLC were investigated utilizing the BiTE-assay system in comparison to the anti-programmed cell death-1 (PD-1) antibody, nivolumab. T-cell signaling molecules were investigated using flow cytometry, ELISA, and qRT-PCR. Tetracyclines were given orally to BALB/c mice engrafted with murine tumor cell lines to study their anticancer effects in vivo, either in the presence or absence of anti-mouse CD8 inhibitors.”
“We found that minocycline enhanced the antitumor activity of T lymphocytes by targeting galactin-1, which is an immunosuppressive protein produced by cancer cells,” said Mari Tone, the primary author of the study.
The researchers discovered that galactin-1 helps cancer cells hide from the immune system by preventing cytotoxic T lymphocytes from reaching the tumor. After tetracycline treatment, galactin-1 lost its ability to prevent T cells from attacking the tumor. The researchers believe that inhibiting galactin-1 could be the key to future cancer treatments.
“These antibiotics have a different mechanism of action from immune checkpoint inhibitors and other immunotherapies used to treat cancer,” stated corresponding author Kota Iwahori.
The researchers believe that their findings may lead to the development of novel medications that target alternative immune pathways and can help cancer patients, particularly those who do not respond to conventional immunotherapies.