How do cytotoxic T lymphocytes (TILs) play a role in ovarian cancer outcomes? What underlying biological activities or cellular interactions help stimulate TILs to destroy or damage cancerous cells? According to News Medical, researchers from Ludwig Cancer Research, an international community of scientists determined to manage and find better solutions to addressing cancer, recently dove deeper into finding the answers to these questions.

Within their research study, the researchers sought to understand two things. First, the researchers wanted to learn how TILs attacked or destroyed ovarian tumors. Secondly, the researchers wanted to learn whether TIL activation could improve the effectiveness of immunotherapy treatments. Take a look at their full findings published in Cancer Cell. 

Ovarian Cancer

As the name suggests, ovarian cancer begins in the ovaries, almond-shaped female organs which produce hormones (estrogen, progesterone) and store eggs. Ovarian cancer comes in different forms, such as germ cell carcinoma tumors (5% of diagnoses), epithelial tumors (90% of diagnoses), stromal carcinoma tumors (5% of diagnoses), and small cell carcinoma of the ovary (0.1% of diagnoses). This malignant cancer can spread to other areas of the body, such as the lungs and liver, lymph nodes, or bowel or abdominal lining. While doctors do not know what causes ovarian cancer in a large percentage of cases, some patients develop this cancer due to BRCA1 or BRCA2 gene mutations. Ovarian cancer symptoms include:

• Abdominal distention and swelling
• Pelvic pain
• Appetite loss
• Menstrual irregularities
• Abnormal vaginal secretions
• Changes in urinary urgency or frequency
• Breast tenderness
• Abnormal uterine bleeding
• Bloating
• Endometrial hyperplasia
• Virilizing symptoms due to testosterone increases

T Lymphocytes (TILs) 

So within this study, researchers wanted to understand how TILs worked to destroy cancer cells. In particular, the focus was on cancerous cells within tumor islets. Prior research highlighted how increased TIL levels in patients with ovarian cancer correlated with increased overall survival. By learning how TILs could manage an immune attack on ovarian cancer, researchers could better determine potential therapeutic options for patients with treatment-resistant cancer. You see, despite the fact that therapeutic options do exist, many forms of this cancer are often difficult to treat with the current standards-of-care (anti-PD-1 checkpoint blockade immunotherapy). 

To begin, researchers sourced different high-grade ovarian cancer samples from patients. They found that antigen presenting cells (APCs) help prompt TILs to attack cancerous cells by stimulating CD28 protein activity. TILs within the ovarian tumor were most effective in attacking the tumors through either APCs and cancer antigens, presenting a two-pronged approach. APCs activate TILs through CD28; using anti-PD-1 immunotherapy increases the efficacy by stopping the “brakes” PD-1 usually places on anti-tumor activity. 

Thus, immunotherapy, in conjunction with APC and CD28 engagement, could heavily increase treatment efficacy. More so, researchers found that anti-PD-1 immunotherapy, CD40L (an APC stimulator), and anti-CTLA-4 immunotherapy, used in conjunction with each other, even reactivated exhausted TILs. While more research is needed to see how this could translate into patient care, it does suggest a potentially more effective therapy for ovarian cancer is on the horizon.