2 February 2026

A Breakthrough Approach in Cancer Treatment: Immunotherapy

Health

According to Prof. Dr. N. Faruk Aykan, Faculty Member of the Faculty of Medicine at İstinye University, immunotherapies developed by releasing the suppression on the immune system represent a breakthrough approach in oncology. However, they do not demonstrate the same level of efficacy in every type of cancer and therefore require careful patient selection.

Immunotherapy, one of the most remarkable advances in cancer treatment in recent years, focuses on harnessing the immune system’s ability to combat tumors. Prof. Dr. N. Faruk Aykan explained the complex relationship between cancer and the immune system, recent scientific developments in immunotherapy, and the patient groups in which this treatment is most effective.

The Relationship Between Cancer and the Immune System

Summarizing the interaction between cancer and the immune system, Prof. Dr. Aykan stated:

“The immune system is a highly sophisticated defense mechanism that distinguishes self from non-self and prevents non-self entities from harming the body. Although cancer arises from the body’s own cells, the immune system can recognize and eliminate cancer cells due to the presence of novel antigens (neoantigens). Cancer development largely results from genetic mutations. Mutated genes produce abnormal proteins, which appear as neoantigens not found in normal cells. The higher the antigenic load of a tumor, the more active the immune response. Tumors with dense immune cell infiltration are referred to as ‘hot tumors,’ and immunotherapy is significantly more effective in these tumors compared to ‘cold tumors,’ which have limited immune cell presence.”

“A Breakthrough Approach in Oncology”

Addressing the most significant recent scientific developments in this field, Prof. Dr. Aykan noted:

“One of the most important scientific breakthroughs in recent years was the discovery of cancer treatment through the inhibition of negative immune regulation, which earned James P. Allison and Tasuku Honjo the 2018 Nobel Prize in Physiology or Medicine. To elaborate, the immune system contains an army of T lymphocytes responsible for fighting cancer cells. Cancer antigens are presented to T lymphocytes by dendritic cells in lymph nodes. Activated T cells then migrate to tumor tissue and attack cancer cells. However, mechanisms that suppress active T cells at these stages were discovered. In lymph nodes, the CTLA-4 molecule on T lymphocyte membranes delivers inhibitory signals, while in tumor tissue, the PD-L1 molecule expressed on tumor cell membranes binds to the PD-1 receptor on lymphocytes, similarly suppressing T-cell activity. Following these discoveries, pharmaceutical technologies rapidly developed anti-CTLA-4, anti-PD-1, and anti-PD-L1 agents (monoclonal antibodies). Many immunotherapy drugs have since been investigated in clinical trials, demonstrated efficacy, and received FDA approval. This represents a groundbreaking advancement in oncology.”

How Immunotherapy Differs from Conventional Cancer Treatments

Highlighting the fundamental scientific differences between immunotherapy and conventional cancer treatments, Prof. Dr. Aykan stated:

“The most important distinction is that immunotherapy drugs are not directly cytotoxic. Instead, they indirectly enhance anti-tumor activity by removing inhibitory mechanisms on T lymphocytes, thereby increasing their capacity to eliminate tumor cells. In a sense, immunotherapy supports the T-lymphocyte army in the battle between T lymphocytes and tumor cells. Unlike chemotherapy, immunotherapy does not exert direct cytotoxic effects on healthy proliferating cells.”

Variable Efficacy Across Cancer Types

Discussing the biological factors influencing treatment outcomes, Prof. Dr. Aykan explained:

“Clinical studies have shown that these novel immunotherapy agents produce dramatic responses in certain cancers, while showing little to no effect in others. Key biological determinants include:

Tumors with defective DNA mismatch repair (dMMR), characterized by high microsatellite instability (MSI-H), which respond exceptionally well to immunotherapy. In MSI-H cancers—such as colorectal, endometrial, and gastric cancers—immunotherapy alone has yielded high response rates regardless of tumor origin (tumor-agnostic), with median survival exceeding five years in metastatic disease. Recently, immunotherapy has also been incorporated into neoadjuvant (preoperative) treatment and has enabled organ-preserving approaches, particularly in rectal cancer.

Tumors with high PD-L1 expression (>50%) demonstrate improved outcomes with immunotherapy, while tumors with PD-L1 expression between 1–49% benefit from combined chemotherapy and immunotherapy.

Cancers with high tumor mutational burden (TMB) tend to respond more favorably to immunotherapy.”

Cancer Types with Favorable Outcomes

Prof. Dr. Aykan listed cancer types in which immunotherapy has demonstrated successful outcomes, stating:

“In addition to the tumors mentioned above, immunotherapy has yielded favorable results in malignant melanoma, non-small cell and small cell lung cancers (NSCLC and SCLC), renal cell carcinoma (RCC), triple-negative breast cancer (TNBC), hepatocellular carcinoma (HCC), biliary tract cancers, head and neck cancers, esophageal cancer, and certain types of gastric cancer.”

Regarding patient selection, he added:

“Patients exhibiting these characteristics can be considered suitable candidates. Today, MSI status and PD-L1 expression are routinely evaluated in tumor samples in many pathology laboratories.”

Ongoing Research and Combination Therapies

Touching on ongoing research, Prof. Dr. Aykan noted:

“Immunotherapy has now established itself as a distinct discipline within oncology. Following the COVID-19 pandemic, mRNA vaccine technologies are also being investigated in various cancer treatments. Combination therapies involving immunotherapy and mRNA-based vaccines targeting individual tumor antigens are currently under investigation and hold significant potential for improved clinical outcomes.”

Side Effects and Economic Considerations

Concluding his remarks, Prof. Dr. Aykan emphasized:

“As with all treatments, immunotherapy agents have their own specific side effects, which are closely monitored by treating physicians. These adverse effects are primarily autoimmune in nature and may include autoimmune pneumonitis, colitis, hepatitis, hypothyroidism, and skin rashes. Additionally, the financial toxicity of these therapies should not be overlooked. In our country, reimbursement is limited to a narrow range of indications, and for patients seeking treatment outside these indications, the financial burden can be substantial. These factors should be carefully considered in healthcare policy planning.”