This research at the CNPEM which was published in Nature Communications is the most complete effort to date on the biology of head and neck tumors, which are among the most aggressive forms of cancer
Head and neck cancer is the eighth most common type of cancer worldwide. This type of cancer impacts patient quality of life because of the severity of the disease (with high recurrence rates) as well as the potential side effects of available treatments.
Unfavorable outcomes tend to be associated with metastasis to the lymph nodes, which occurs when the tumor cells spread to the lymphatic ganglia. Lymph nodes are structures that contain immune cells specialized in fighting infection and disease. At this stage of metastasis, patient survival rates drop by approximately 50%.
Detecting the body’s response to the presence of metastasis in the lymph nodes and discovering new biomarkers that can be utilized are challenges to be overcome in order to help manage patients with head and neck cancer.
Proteins connected to microenvironments
The study by researchers at the Brazilian Center for Research in Energy and Materials (CNPEM), an organization under the supervision of the Ministry of Science, Technology and Innovation (MCTI), was published and also selected to appear among the Editors’ Highlights in the journal Nature Communications, and was the first to analyze malignant and non-malignant cells and their respective proteins present in different microenvironments in search of potential patterns that could be associated with the development of lymph node metastases. Samples of tumors, lymph nodes, saliva, and blood from patients with and without metastases (provided by reference hospitals in Brazil and Chile) permitted the researchers to conduct the most complete study on the biology of head and neck cancer to date.
“We investigated tissues and well as biofluids in an attempt to assess differences between patients with and without metastases. We also tried to identify which proteins and cells are responsible for this poor prognosis for head and neck cancer,” explains researcher Adriana Paes Leme (CNPEM/MCTI), who for years has led studies investigating biomarkers and therapeutic targets.
For 10 years, the CNPEM has conducted research looking for biomarkers and therapeutic targets for prognostics and treatment of head and neck cancer. A previous study by the same group, published in Nature Communications in 2018 (https://www.nature.com/articles/s41467-018-05696-2) investigated the tumor microenvironment, comparing the invasive front and the interior of the tumor to select proteins associated with poor prognosis. In this study, a panel of proteins was able to classify patients with and without lymph node metastasis.
In the new study, a groundbreaking strategy was used to isolate different cell populations from tumor and lymph node tissue (malignant and non-malignant cells), providing a better understanding of these populations within the context of metastasis.
“Even though not all the cell populations in the microenvironments are composed mainly of immune cells, they enrich some biological processes related to immune response, showing an interconnection between the different sites,” she explains.
Integrated analyses and innovative strategies
Beyond strategies from proteomics based on mass spectrometry, the most accurate method for quantifying proteins, another unique characteristic of this research was the integration of these data with information from RNA sequencing of unique cells available in public databases, which expanded understanding of the proteomics findings. The use of machine learning was also essential to test pre-defined potential targets in search of prognostic signatures able to classify patients with and without lymph node metastasis.
“We followed various analysis strategies to show that some proteins may be associated with modulation of the immune cells in the different environments. These proteins could be considered potential prognostic markers,” explains Adriana Paes Leme.
The machine learning methods revealed metastatic signatures with high sensitivity and specificity in blood and saliva samples from patients with head and neck cancer which show promise for clinical application.
Next steps
This work creates important fronts for investigation to understand the tumoral microenvironment and identify markers of lymph node metastasis, the main factor in poor prognosis for head and neck cancer. Differential composition of the proteins and immune cells in the different microenvironments creates possibilities to investigate new immunotherapy targets, including some proteins for RNA processing that are expressed by these cells in the immune system. Important information was also obtained about candidates for the development of prognostic tests that can assist in decision making on clinical treatment.
Support and partnerships
The study was a collaboration between researchers from Brazilian universities including USP and UNICAMP, the University of the Andes and University of Talca (Chile), Jundiaí School of Medicine (FMJ), and institutions like the Brazilian Cancer Institute (INCA), São Paulo State Cancer Institute (ICESP), A.C. Camargo Cancer Center, and Hospital Israelita Albert Einstein. The study was funded by the CNPEM, the São Paulo Research Foundation (FAPESP), and the Brazilian National Council for Scientific and Technological Development (CNPQ). Through the Brazilian Ministry of Health’s National Cancer Care Program (PRONON), this line of research on head and neck tumors at LNBio receives funding from the CPFL and Colgate companies.
CNPEM campus
About CNPEM
Sophisticated and effervescent environment for research and development, unique in Brazil and present in few scientific centers in the world, the Brazilian Center for Research in Energy and Materials (CNPEM) is a private non-profit organization, under the supervision of the Ministry of Science, Technology and Innovation (MCTI). The Center operates four National Laboratories and is the birthplace of the most complex project in Brazilian science – Sirius – one of the most advanced synchrotron light sources in the world. CNPEM brings together highly specialized multi-thematic teams, globally competitive laboratory infrastructures open to the scientific community, strategic lines of investigation, innovative projects in partnership with the productive sector and training of researchers and students. The Center is an environment driven by the search for solutions with impact in the areas of Health, Energy and Renewable Materials, Agro-environment, and Quantum Technologies. As of 2022, with the support of the Ministry of Education (MEC), CNPEM expanded its activities with the opening of the Ilum School of Science. The interdisciplinary higher course in Science, Technology and Innovation adopts innovative proposals with the aim of offering excellent, free, full-time training with immersion in the CNPEM research environment. Through the CNPEM 360 Platform, it is possible to explore, in a virtual and immersive way, the main environments and activities of the Center, visit: https://pages.cnpem.br/cnpem360/
