Treatment Strategies for Mouth Cancer via Immunotherapy

Treatment Options for Mouth Cancer via Immunotherapy

Oral cancer, a group of malignancies that can occur in any part of the mouth, is a significant health concern. Fortunately, advancements in medical research have led to the development of immunotherapy as a promising treatment option.

Immunotherapy for oral cancer works by stimulating or blocking the action of certain immune system molecules, helping the body's immune system recognize and fight cancer cells more effectively. This approach offers a multifaceted strategy: cell-based therapies and adoptive cell transfer enhance specific immune cell attack; monoclonal antibodies unblock immune evasion pathways; cytokine therapies remodel the immune microenvironment; and vaccines prime the immune system to recognize the cancer more effectively.

Cell-based therapies involve using immune cells that are either extracted, expanded, and reinfused or genetically engineered to target cancer cells. Adoptive cell transfer (ACT) includes tumor-infiltrating lymphocytes (TILs), T cell receptor-engineered T cells (TCR-T), and chimeric antigen receptor T cells (CAR-T). These autologous T cells are cultivated or modified in vitro to specifically recognize and kill tumor cells upon reinfusion.

Monoclonal antibodies (mAbs) are designed to target specific molecules on cancer cells or immune checkpoints that cancer cells exploit to evade immune attack. Blocking inhibitory receptors such as TIGIT on T cells and NK cells with monoclonal antibodies can restore their anti-tumor activity, thereby enhancing the immune response against oral cancer.

Adoptive cell transfer therapy specifically refers to the harvesting, modification, expansion, and reinfusion of immune cells such as TILs, TCR-T cells, or CAR-T cells to enhance tumor recognition and killing. Human trials in other solid tumors have shown promise, and therapies like lifileucel (TIL based) and afamitresgene autoleucel (TCR-T) have FDA accelerated approvals for melanoma and solid tumors in 2024, with potential relevance to oral cancers.

Cytokine modulation therapy uses cytokines such as interleukin-12 (IL-12) and IL-18 produced by dendritic cells or administered therapeutically to boost the immune environment surrounding tumors. For instance, IL-12 enhances T cell infiltration and activity within tumors by stimulating NK, cytotoxic T lymphocytes, and Th1 cells, and it also upregulates MHC class I expression on tumor cells for better recognition.

Vaccines present tumor antigens to educate and activate T cells and other immune cells against oral cancer. DCs can be loaded with tumor neoantigens or genetically modified to overexpress immunostimulatory cytokines, promoting robust and durable anti-tumor immunity. Combining vaccines with immune checkpoint inhibitors can further enhance efficacy.

It is important to note that immunotherapy for oral cancer may be delivered by various routes, including intravenous, subcutaneous, intralesional (directly into the tumor), oral, or topical, depending on the formulation and cancer type.

Other treatment options for oral cancer include surgery, radiotherapy, and chemotherapy. Early detection and proper treatment are essential for positive outcomes in oral cancer. Anyone with symptoms such as painful or persistent sores or bleeding in the mouth, difficulty chewing or swallowing, jaw pain, or earaches should seek medical attention.

In the United States, there are approximately 53,000 new cases of oral cancer annually. Other types of oral cancer include verrucous carcinoma, salivary gland malignancies, melanoma, sarcoma, adenocarcinoma, and lymphoma. After immunotherapy, a person may need regular checkups and tests to monitor their condition.

Traditional treatment options for oral cancer include surgery, chemotherapy, radiotherapy, or a combination of these treatments. Radiotherapy uses high-energy X-rays to kill cancer cells and shrink tumors. The most common type of oral cancer is squamous cell carcinoma.

During cancer treatment, eating softer foods, avoiding very hot or cold foods, using soothing mouthwashes, practicing relaxation techniques, getting enough rest, and using medications for pain or flu symptoms can help manage side effects. If side effects become too uncomfortable, it is important to seek medical advice.

Immunotherapy treatments can be received at a clinic or outpatient unit in a hospital, or at home, depending on the type. Treatment for mouth cancer depends on the type and size of the cancer, the grade and stage of cancer, and the person's general health.

References:

National Cancer Institute (2021). Cancer Immunotherapy.
Cancer Research UK (2021). Immunotherapy for cancer.
Nature Reviews Cancer (2020). Combinations of immunotherapy and radiotherapy for cancer.
Cell (2020). TIGIT blockade enhances anti-tumor immunity in preclinical models and clinical trials.
Cancer Immunology Research (2019). Systemic administration of IL-12 enhances tumor-specific CD8+ T cell responses and improves survival in a murine oral cancer model.