Squamous cell carcinoma (SCC) is a common cancer that can develop on the skin or moist linings of the body, such as the mouth, throat, or genital area. While many cases are localized and treatable with conventional methods, advanced forms can spread and become challenging to manage. Immunotherapy has emerged as an innovative treatment approach, harnessing the body’s own immune system to recognize and combat cancer cells. It represents a significant advancement, offering new possibilities for patients facing advanced or recurrent SCC.
How Immunotherapy Targets Cancer Cells
The immune system has checks and balances, known as “checkpoints,” which prevent it from mistakenly attacking healthy cells. These checkpoints involve proteins on immune cells that act like “off” switches, ensuring a controlled immune response. Cancer cells, including those in SCC, can exploit these natural safeguards by displaying certain proteins on their surface that engage these checkpoints, effectively “hiding” from detection by immune cells, particularly T-cells.
A key pathway involves programmed cell death protein 1 (PD-1) on T-cells and its ligand, programmed cell death ligand 1 (PD-L1), often present on tumor cells. When PD-1 binds to PD-L1 on a cancer cell, it sends an inhibitory signal that prevents the T-cell from destroying the tumor. Immunotherapy drugs, specifically checkpoint inhibitors, block this interaction. By disrupting the PD-1/PD-L1 pathway, these drugs remove the “brakes” on the immune system, allowing T-cells to activate, identify cancer cells, and mount an effective anti-tumor response, thereby enabling the body’s defenses to target and eliminate malignant cells.
Common Immunotherapy Medications
Several immunotherapy medications have gained approval for treating various forms of squamous cell carcinoma. Cemiplimab (Libtayo) was the first agent approved by the FDA for advanced cutaneous SCC, including metastatic or locally advanced cases unsuitable for surgery or radiation.
Pembrolizumab (Keytruda) is another checkpoint inhibitor widely used in SCC treatment. It is approved for patients with recurrent or metastatic cutaneous SCC that cannot be cured by surgery or radiation. Pembrolizumab is also approved for certain types of head and neck squamous cell carcinoma (HNSCC), particularly when the cancer has spread or returned after prior treatments. Cosibelimab (Unloxcyt) is approved for advanced cutaneous SCC. Nivolumab (Opdiva) is also approved for metastatic HNSCC, especially for patients whose disease progressed after chemotherapy.
Patient Candidacy for Immunotherapy
Immunotherapy is not typically the initial treatment for early-stage squamous cell carcinoma, which often responds well to surgical removal or radiation. Instead, it is reserved for more advanced situations where the cancer has spread to distant sites, recurred after previous treatments, or is locally advanced and cannot be effectively removed by surgery or treated with radiation. It is often considered when surgical intervention would lead to significant functional or aesthetic consequences, or when complete surgical resection is not feasible.
Doctors also consider specific tumor characteristics. Testing for biomarkers, such as PD-L1 expression on tumor cells, can offer insights into treatment benefit. While PD-L1 expression is a predictive marker, it is not the sole determinant; a full assessment of the patient’s overall health and cancer characteristics guides decisions. Certain patient populations, such as those with weakened immune systems or organ transplants, may require careful evaluation due to potential risks.
Managing Potential Side Effects
Immunotherapy works by activating the immune system, which can sometimes lead to side effects known as immune-related adverse events (irAEs). These events occur when the activated immune system inadvertently targets healthy tissues and organs. The nature and severity of these side effects vary depending on the specific drug and the individual patient.
Common irAEs include fatigue, skin rashes, and itching, often mild to moderate. Patients might also experience diarrhea or inflammation in various organs. Less common but more serious side effects can involve inflammation of the lungs (pneumonitis), colon (colitis), liver (hepatitis), or hormone-producing glands such as the thyroid or pituitary. Patients receiving immunotherapy should promptly report any new or unusual symptoms to their medical team. Early recognition and management of these side effects, often involving corticosteroids or other immunosuppressants, are important to minimize their impact and allow treatment to continue safely.
Treatment Response and Expectations
Patients undergoing immunotherapy for squamous cell carcinoma can experience a range of outcomes. A “response” typically means the tumor has either shrunk significantly or stabilized, preventing further growth. Studies show that a proportion of patients with advanced SCC respond to immunotherapy, with some achieving a complete pathological response where no viable tumor cells are found at surgery. For instance, objective response rates for cemiplimab and pembrolizumab in advanced cutaneous SCC have ranged from approximately 34% to 50% in some trials.
While immunotherapy can lead to durable responses in some individuals, it does not work for every patient. The treatment is typically administered as an intravenous (IV) infusion, with dosing schedules varying, often every few weeks. Continuous monitoring of the patient’s response and any potential side effects is standard, with imaging scans and clinical assessments performed periodically to track progress.