Mesothelioma: A Study of T-Cell Infiltration As the Disease Evolves

 

The history of mesothelioma dates back to 1767 as being the earliest record of tumors found on the lining of the lungs. In 1909 J.G. Adami introduced the term “mesothelioma” as it forms in the mesothelium, which is the protective layer surrounding internal organs.

According to the Journal of Clinical Oncology, mesothelioma represents only .03% of cancers diagnosed in the U.S. Because it is so rare, mesothelioma has been misdiagnosed for decades. Although it was first linked to asbestos exposure around 1930, it was not until the 1960s that in-depth research began on the disease and its association with asbestos.

The Latency Period

The medical profession has not yet discovered an accurate method of early diagnosis. Therefore, mesothelioma is usually diagnosed in the latter stages of its long latency period. It can take anywhere from fifteen to seventy years after exposure to asbestos for the disease to develop.

Only about 15% to 20% of people with pleural mesothelioma, which is the most common type, qualify for surgeries that could add several years to the average one-year prognosis.

Malignant pleural mesothelioma (MPM) is an aggressive cancer in the lining of the lungs caused by exposure to asbestos. Symptoms involve shortness of breath, cough, fluid in the lungs, and chest pain. MPM accounts for up to seventy-five percent of mesothelioma cases.

Asbestos fibers can lodge in the lining of the lungs and cause inflammation and scarring.

The standard of care has been chemotherapy until the recent introduction of immunotherapy, which improved survival. Immunotherapy and chemotherapy influence the environment around the tumor. This includes, but is not limited to, immune cells, blood vessels, fibroblasts, signaling molecules, and extracellular matrix.

About the Study

The primary goal of the study was to observe changes in the tumor environment during mesothelioma and also in post-systemic (involving the whole body) therapies from paired samples.

Samples from twenty matched formalin-fixed paraffin-embedded tissue (FFPE) from ten MPM patients (median age 62) were examined both at diagnoses and followed-up at disease progression. This included untreated samples and samples that were treated with immunotherapy or chemotherapy.

Paraffin-embedded tissues are methods used to preserve samples for research.

Tissue densities of immune effector cells that react defensively during an immune response, were measured through image analysis.

Study Results

All patients had been diagnosed with epithelioid histology (having epithelioid characteristics). Three of the matched samples were from patients who had not received treatment between biopsies.

The remaining seven pairs of samples were from patients who had been treated with either immunotherapy, chemotherapy, or both.

Conclusions:

Since the approval in 2004 of pemetrexed plus cisplatin, no new MPM drugs have received full approval. However, new therapeutic targets and a new understanding of the biology of mesothelioma have proven to be significant advances.

The researchers observed immune cell changes during MPM evolution that tended to decrease after systemic therapy. The team recommends further investigation to determine the optimum time that immunotherapy may be needed.

 

Rose Duesterwald

Rose Duesterwald

Rose became acquainted with Patient Worthy after her husband was diagnosed with Acute Myeloid Leukemia (AML) six years ago. During this period of partial remission, Rose researched investigational drugs to be prepared in the event of a relapse. Her husband died February 12, 2021 with a rare and unexplained occurrence of liver cancer possibly unrelated to AML.

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