For cancer patients, immunotherapy is now more than just a dawn, it is a road to recovery and prosperity. Anti-PD treatment continues to play a role in a variety of cancers including lung cancer and melanoma. Combined with radiotherapy and chemotherapy, immunotherapy can often increase the effective rate of treatment by 50-60%. On the other hand, CAR-T cell therapy continues to exert positive effect on hematoma. After long-term observation, the probability of long-term survival is as high as 81% (one-year survival rate) for patients who respond completely to CAR-T cell therapy.

Whether it is anti-PD therapy or CAR-T cell therapy, its essence is to relieve the inhibition of T cells and activate T cells, making it stronger and thus capable of killing cancer cells. In previous studies, we found that in the vicinity of tumor cells, there are many T cells already going around the tumor tissue (these T cells are what we often call tumor infiltrating T cells), but they do not kill cancer cells at all. Why is this?

The latest study published in Nature by Ton N. Schumacher’s team from the Netherlands Cancer Institute (NKI) shows that only about 10% of T cells can recognize tumor tissue at the tumor site, and the rest just act as “bystanders”!

How does T cells recognize tumor cells? Mostly they rely on T cell receptors on T cells, which is what we often call TCR, to recognize a wide variety of different cells. Whether the cell is good or bad is identified by the TCR and the cell surface-identifying substance (MHC peptide). To put it more simply, when the police encounter a person of unknown origin, they will check our identity card (MHC) with an authentication machine (TCR). If our ID card is legal, it will be safe and the T cell will not be good. The mutant cells, such as cancer cells, are cleared directly.

In the previous study, we found that there are many infiltrating T cells around the tumor, but why are the tumor cells not destroyed? That's because these T cells simply can't recognize these tumor cells! In the TCR test of breast cancer and colorectal cancer, the researchers found that in the TCR detection of T cells around the tumor, only one of the 20 TCRs can activate T cells to kill cancer cells!

In further studies, the researchers did not find TCRs that recognize cancer cells in tumor infiltrating T cells from two other patients. Therefore, although there are tumor infiltrating T cells, it still cannot effectively kill tumors. In the overall data measurement, the killer T cells that can recognize the tumor tissue occupy only about 10% of the total.

These data suggest that the ability of T cells to recognize adjacent tumor tissue in tumors may not be as common as we know, and the lack of TCR diversity will greatly limit the therapeutic effects of tumors. At the same time, these studies have also shown that if the coverage of TCR is sufficiently broad, then when anti-PD treatment is used to relieve tumor microenvironment inhibition, T cells can help T cells better kill tumor cells, thus enhancing the effect of anti-PD treatment.

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