A look into Lacrimal Gland Adenoid Cystic Carcinoma and Its Tumor Immune Microenvironment
Adenoid cystic carcinoma of the lacrimal gland, known as LGACC, is the most common malignant tumor originating from the epithelial cells of the lacrimal gland. Despite multimodal treatments like surgery and radiation, it remains highly aggressive and difficult to cure. Scientists believe that the tumor's structure, known as its pathological subtype, and its interaction with the immune system both play critical roles in how the disease progresses.
The Study Approach
Researchers retrospectively studied tumor samples from eighteen patients with LGACC treated between 2012 and 2021. They classified each tumor into one or more pathological subtypes and also investigated the tumor immune microenvironment, or TIME, using advanced imaging and immunochemistry techniques. Their goal was to see how tumor patterns and immune activity relate to patient survival.
Different Pathological Subtypes and Their Impact
The tumors showed a mix of different subtypes. The cribriform pattern was the most common, making up 39 percent of tumor areas, followed by tubular at 19 percent, basaloid at 17 percent, and a mixed cribriform-tubular (C+T) type at 14 percent. Sclerosing and comedocarcinoma types were rare, together making up just 11 percent. Importantly, patients whose tumors were dominated by the cribriform subtype had better overall survival, while those dominated by the basaloid subtype had worse outcomes.
Immune Cell Infiltration Patterns
When examining immune activity, researchers found that most immune cells were located at the tumor margins — the areas where the tumor meets normal tissue — rather than deep inside the tumor. Using the CD45 marker to identify immune cells, they categorized tumor regions into "clustered," "sparse," or "non-infiltrated" based on the density of immune cells. The cribriform subtype showed the highest level of immune cell infiltration, while the basaloid subtype had the least.
Tumor Immune Microenvironment
Through multiplex immunochemistry, researchers mapped the specific types of immune cells present. CD8+ T cells, known for their ability to kill cancer cells, were most abundant in the tumor margins and cribriform areas. CD4+ T cells were also highly present across different tumor types, supporting immune responses. Very few natural killer (NK) cells were found, and macrophages, especially the M2 type which tends to suppress immune responses, were more common in the basaloid subtype.
Key Findings About Prognosis
The study confirmed that tumors with a cribriform-dominant structure not only had better immune cell infiltration but were also associated with better patient survival. In contrast, tumors dominated by the basaloid subtype had weaker immune infiltration and worse outcomes. This suggests that the tumor's microscopic structure can predict how the immune system responds and how aggressive the cancer will be.
Why This Matters
This research highlights that not all LGACCs are the same. The immune environment inside and around a tumor changes depending on the tumor's subtype. Understanding these patterns could guide the development of new therapies, especially immunotherapies that activate the body's natural defenses against cancer. Targeting specific immune cells like CD8+ T cells or reprogramming macrophages could be strategies for future treatment.
Future Directions
Although this study offers valuable insights, the sample size was small. Future research with larger patient groups and more advanced techniques like spatial transcriptomics could provide deeper understanding. Clinical trials tailored to different immune profiles, especially targeting the differences between cribriform and basaloid tumors, could help improve outcomes for patients with this challenging disease.
To learn more, check this out! Tumor immune microenvironment in adenoid cystic carcinoma of the lacrimal gland: relationship with histopathology and prognosis | BMC Cancer | Full Text
