Yale scientists have investigated how a subset of specific T cells survive a microenvironment within a tumor throughout the progression of the cancer.
Precursor stem-like CD8+ T cells help to sustain anti-tumor T cell responses and promote effective immunotherapy treatment response. Although tumor cell signals cause T cells to differentiate, making them ineffective against tumors, a population of the stem-like T cells is maintained.
However, they are actually precursors to those that ultimately become ineffective. The mechanism by which this population of cells is maintained has not been well understood. Scientists from Yale University sought out to determine how these cells are maintained long term with the hopes that the information may be used to develop more effective anti-tumor immunotherapies.
In their quest, the researchers conducted a study on mice that were genetically engineered to develop tumors. Lung tumors were induced in the mice via intratracheal infection with adenovirus vector and treated with doxycycline and tamoxifen. The stem-like CD8+ T cell subset was tracked throughout tumor development using molecular analysis and cell microscopy techniques. Bioinformatics methods were used to analyze the data.
The results of the study showed that the stem-like T cells are maintained outside of the tumor microenvironment, within draining lymph nodes. These draining lymph node cells remain unchanged transcriptionally and phenotypically, and they do not become exhausted, as do the intratumoral T cells. These cells, therefore, may have the capacity to respond to cancer immunotherapy.
The researchers also studied whether draining lymph node T cells have relevance in human patients with lung adenocarcinoma. They use published RNA sequencing data from studies that involved biopsied lung tissues and lymph nodes of healthy patients and those with lung adenocarcinoma. After using bioinformatics to catalog and group CD8+ T cells from the different tissues, they found that stem-like CD8+ T cells were present in the lymph nodes of patients with lung adenocarcinoma; therefore, this cell population may also be important in the case of human cancers. The draining lymph node cell population may be crucial for maintaining anti-tumor activity and could be targeted to develop novel cancer immunotherapies.
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Connolly, K., Kuchroo, M., Venkat, A., Khatun, A., Wang, J., & William, I. et al. (2021). A reservoir of stem-like CD8 T cells in the tumor-draining lymph node maintains the ongoing anti-tumor immune response. doi: 10.1101/2021.01.27.428467
Flores, K. (2021). Yale researchers discover reservoir of T cells involved in anti-tumor response. Retrieved 2 March 2021, from https://yaledailynews.com/blog/2021/02/14/yale-researchers-discover-reservoir-of-t-cells-involved-in-anti-tumor-response/