Home Research paper Immune cells found in tumors of head and neck cancer patients, study reports show

Immune cells found in tumors of head and neck cancer patients, study reports show

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A new study by scientists at the Emory Vaccine Center and the Winship Cancer Institute at Emory University reports that immune cells that are the primary targets of immune checkpoint inhibitors are present in the tumors of patients with head and neck cancer.

The study focuses on head and neck tumors that are positive for the human papillomavirus (HPV), which is becoming one of the most common types of head and neck cancers treated in the Western world . The results should be published in Nature.

He suggests that checkpoint inhibitors, which have transformed the treatment of several types of cancer, may be particularly effective against this type of head and neck cancer. The results also indicate that the experimental approach to therapeutic vaccination against HPV + cancer could be broadened to include more elements of the virus, potentially triggering a broader and stronger immune response.

Researchers in Rafi Ahmed’s lab at the Emory Vaccine Center collaborated with co-chairs of the Winship Head and Neck Cancers working group, oncologists Nabil Saba, MD and Mihir Patel, MD, to obtain samples from patients with head tumors and neck at the start of the course. treatment.

About five years ago we started to have an influx of patients who sought our center for surgical treatment. We often heard a variation of a similar story: I was sick with cold-like symptoms and once that resolved I noticed swelling in a lymph node on the side of my neck. Stories like this got us thinking about how the immune system might play a unique role, different from typical head and neck cancers linked to smoking.. “

Mihir Patel, MD, Oncologists, Emory Health Sciences

The team wanted to learn more about the different types of CD8 or “killer” T cells found in cancers; CD8 T cells are specialized immune cells capable of detecting and killing virus-infected or tumor-infected cells, if they are not constrained by regulatory signals. The inhibitory PD-1 receptor is highly expressed on depleted CD8 T cells in chronic viral infections and cancer, and rod-like PD-1+ CD8 T cells are crucial for maintaining tumor-specific CD8 T cell responses. The majority of currently available checkpoint inhibitors, such as pembrolizumab and nivolumab, block the PD-1 signaling pathway.

“Our results show that a subset of HPV-specific CD8 T cells in the tumor bears a striking resemblance to the strain-type CD8 T cells that our laboratory previously defined in mouse models as proliferating in response to PD blockade. -1 “, explains Andreas. Wieland, PhD, co-lead author of the article and instructor in Ahmed’s lab.

“It is reasonable to assume that these cells would similarly provide a proliferative surge in response to PD-1 blockade in these patients. However, this remains to be formally tested.”

HPV-positive tumors have a relatively good response to conventional forms of treatment such as radiation therapy and chemotherapy, Wieland adds. The group of patients studied at Winship were treatment-naïve when tumor samples were obtained; how radiation therapy and chemotherapy affect the number and phenotype of T cells in the tumor requires further research.

“These results significantly improve our understanding of CD8 T cell responses in the tumor microenvironment in HPV-related oropharyngeal cancers, and possibly other viral-mediated tumors,” said Saba. “This confirms the existence of the different lineages necessary for an effective anti-tumor response specific to T cells. Taking advantage of the local immune response by avoiding its possible early elimination by traditional therapeutic modalities may pave the way for a better clinical outcome for patients This may have implications for how best to incorporate immunotherapy into the treatment of other viral-mediated tumors. “

“We now tend to think that incorporating immune therapy with PD-1 blockade before surgery or radiation therapy may be of benefit to patients,” Patel said. “We are actively developing ‘window of opportunity’ studies to understand this.

By examining both primary tumors and metastatic lymph nodes, the researchers were able to detect both tumor-specific strain-like CD8 T cells, which can proliferate in response to HPV peptides, and more differentiated cells in terminal phase that do not proliferate. Unlike the significant numbers of tumor-specific CD8 T cells in tumors, tumor-specific cells have appeared in very low abundance in the blood of patients, suggesting that they preferentially reside in tumors.

The team also found that the different CD8 T cell subsets in the tumor microenvironment differ in their location, with stem cells residing in distinct niches in the stroma and far from the tumor cells themselves.

The focus on HPV-positive tumors in this study facilitated the study of tumor-specific T cells with defined specificities in several patients because the virus provides a defined set of tumor associated antigens, while in Other types of cancer, the antigens caused by mutations will vary from individual to individual.

Source:

Journal reference:

Eberhardt, CS, et al. (2021) HPV-specific PD-1 + strain-like CD8 T cells functional in head and neck cancer. Nature. doi.org/10.1038/s41586-021-03862-z.