Science Sub-Journal: Differences in T cell functional status determine resistance to cancer treatment

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer in humans

In a new study published in the journal Science Immunology on October 29, a team led by Brendan Horton, a postdoctoral fellow in Spranger's laboratory, revealed the reasons why T cells did not respond to ICB and proposed A possible solution was proposed

Scientists have long believed that the conditions inside the tumor determine when T cells stop working and become exhausted after overstimulating or working too long to fight the tumor

The senior author of the study, Spranger, said that the concept of the dysfunctional state that leads to ICB resistance before T cells enter the tumor is quite novel

She said: "We show that this state is actually a preset state, T cells have no response to treatment before entering the tumor

To determine why some tumors are resistant to ICB, Horton and the research team studied T cells in a mouse model of non-small cell lung cancer

Seq-Well reveals different gene expression patterns between responsive and non-responsive T cells

Now that Horton and his colleagues have a possible explanation for why some T cells do not respond to ICB, they decided to see if they can help anti-ICB T cells kill tumor cells

Cytokine therapy for human patients is currently not safe because cytokines can cause serious side effects and a reaction called "cytokine storm", which can cause severe fever, inflammation, fatigue, and nausea

"This may be transformed into a treatment method to improve the treatment response rate of non-small cell lung cancer

Spranger agrees that this work will help researchers develop more innovative cancer treatments, especially because researchers have traditionally focused on T cell failure rather than the early role that T cell functional status may play in cancer

She said: "If T cells are dysfunctional in the early stage, ICB will not be effective.

Jeffrey Bluestone, Distinguished Professor of Metabolism and Endocrinology at the University of California-San Francisco, agrees, and he was not involved in the study of this paper