Immunotherapy and Its Role in Lung Cancer

Cancer is one of the most fatal disorders of present times. Lung cancer is the second most common cancer in the world. Around 2.21 million new cases of lung cancer had been detected in 2020. Every year around 1.8 million people lose their lives because of lung cancer. Over the years, scientists have come across different treatment protocols for cancer treatment. The use of immunotherapy is one such technique to fight against cancer.

What Is Lung Cancer?

Abnormal cell division of the lung parenchyma is responsible for lung cancer. This excessive and abnormal proliferation of lungs is associated with the formation of dysplastic changes in the lung tissue (abnormal cell morphology, abnormal cellular function, and abnormal size and shoes of the nucleus).

The most common cause of lung cancer is smoking. Any form of smoking is associated with the ingestion of various carcinogenic substances. Various carcinogens present are polycyclic aromatic, hydrocarbons (PAHs), aromatic amines, N-nitrosamines, benzene, vinyl chloride, arsenic, and chromium in the smoke. These substances are responsible for DNA (deoxyribonucleic acid) damage and changes in cellular metabolic activity.

Occupational carcinogens like asbestos, beryllium, cadmium, bismuth, chloromethyl, ethers, chromium, nickel, radon, silica, and vinyl chloride are also associated with lung cancer. Other than this, indoor pollution from smoke and outdoor pollution is responsible for 17 percent of cancers in non-smokers. This type of pollution is also called secondhand smoke pollution.

Genetic and familial factors are also associated with 8 percent of cases of lung carcinoma. The most prominent gene associated with lung cancer is the RAS (proteins) gene. Also, mutation of tumor protein p53, microRNAs, and ROS1 is associated with the formation of lung cancers. Mutation of epidermal growth factor receptor (EGFR) is linked to the development of lung cancer in female non-smokers.

Infections are also closely related to the formation of lung cancer. Bacterial infection caused by chlamydia pneumonia is associated with lung cancer. Apart from this, viruses like the Epstein-Barr virus and human papillomavirus (HPV) are responsible for lung cancer.

The Clinical Manifestations of Lung Cancer Are:

1. Difficulty in breathing even after normal activity and history of respiratory distress.

2. Heavy coughing, accompanied by a wheezing sound.

3. Presence of blood with coughing.

4. Chest pain and heaviness in the chest.

5. Weight loss.

What Is Immunotherapy?

The microenvironment of the cancer cells is comprised of different cell types like precursors, pericytes, myeloid-derived suppressors cells (MDSCs), cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), T and B lymphocytes, NK cells, and dendritic cells. These cells can suppress immune cell expression and can escape immune surveillance. This is essential for the progression of cancer cells. The mechanisms behind these processes are:

• Resistance of the tumor cells due to deficient expression of the major histocompatibility complex (MHC).

• Release of the cytokines, which are immunosuppressive.

• Death of the T lymphocytes.

Immunotherapy is a treatment method in which the immunity system of the body is activated and is used to kill cancer cells. Dr. William B. Coley first proposed the use of such therapy in cancer treatment.

Immunotherapy for cancer treatment can be categorized into three types. These are:

1. Immune Checkpoint Inhibitors: PD-L1 protein and the PD-1 receptor prevent the immune system from interacting with the cancer cells. These types of drugs prevent this interaction and let the immune cells attack the cancer cells.

2. Cancer Vaccines: These are not cancer-preventing vaccines. But vaccines target the proteins present in the cancer cells and make them susceptible to the immune system.

3. Adoptive T Cell Therapy: The death of the T cell is one of the main features of lung cancer. In these conditions functionality of the T lymphocytes is increased through laboratory techniques, and they are administered into the body to kill cancer cells.

What Are the Immune Checkpoint Inhibitors?

This group of drugs interacts with PD-1 and CTLA-4 molecular pathways. Different drugs belong to this group are:

1. Anti-CTLA-4: These are the monoclonal antibody that acts against CTLA-4 pathways. Ipilimumab is a drug belonging to this group and is mainly used in the treatment of non-small cell lung cancer.

2. Anti-PD-1 and Anti-PD-L1: The programmed death receptor 1 (PD-1) is present in the T lymphocytes, B lymphocytes, natural killer cells, and activated monocytes. PD-L1 proteins present in the cancer cells bind to these receptors and escape the immune system. Drugs like Durvalumab, Atezolizumab (both of these drugs act against PD-L1 patients) or Nivolumab, and Pembrolizumab (these two are anti-PD-1 rector drugs) block this pathway and cause the destruction of cancer cells.

What Are Cancer Vaccines?

These vaccines produce antigen-specific antibodies, CD4+ T helper cells, and CD8+ cytotoxic T-lymphocytes that act against tumor-associated antigens. Different types of drugs belong to this group are:

1. MAGE-A3 Vaccine: MAGE-A3 antigen is expressed in almost every type of lung carcinoma. MAGE-A3 antigen-specific antibody is composed of recombinant fusion proteins. This vaccine is used as an adjuvant in postoperative conditions or treatment of early cases of lung cancer.

2. Epidermal growth factor (EGF) Vaccine: EGF is a well-known oncogenic factor whose over-expression is related to the aggressiveness of cancer. This factor is associated with cellular proliferation, metastasis, and angiogenesis. CIMAvax-EGF vaccine is made up of human recombinant proteins that block the action of epidermal growth factor. This vaccine is used for advanced cases of lung cancer.

3. Belagenpumatucel-L: This is an allogenic lung cancer vaccine that is derived from the cell lines of the four types of lung cancer cells. Transforming growth factor beta is a cytokine that is essential for the cellular proliferation of cancer cells. Excessive levels of transforming growth factor-beta are responsible for immune suppression in these cases. This vaccine can downregulate the functioning of the transforming growth factor beta.

4. Liposomal BLP25: Mucinous glycoprotein-1 (MUC-1) is a tumor-associated antigen commonly found in non-small cell lung cancer cases. Structurally these glycoproteins are different than normal MUC-1 proteins. The BLP25 liposome vaccine (L-BLP25) or Tecemotide is composed of 25 different types of amino acids. This vaccine prevents the over-expression of MUC-1. Another vaccine that acts against the overexpression of MUC-1 is the TG4010 vaccine.

What Is Adoptive Cell Therapy?

This is a type of passive immunotherapy. Lymphokine-activated killer (LAK) cells were first identified in 1982. These cells can kill cancer cells in stimulated conditions. Administration of recombinant IL-2 (rIL-2) and transfusion of autologous or allogeneic (derived from the same spices) LAK cells can be used in the treatment of advanced cases of lung cancer. Autologous natural killer T (NKT) cells and cytokine-induced killer (CIK) cells can also be used to treat cancer cases.

How Is It Used?

Most of the drugs used in immunotherapy are used in advanced cases of lung carcinoma. Sometimes these drugs are used in combination with chemotherapeutic drugs. In some cases, such drugs can be postoperative conditions.

What Are the Side Effects?

Immunotherapeutic drugs do not show major side effects. The potential side effects are swelling, redness, and itching in the skin. Other than this, patients can complain of symptoms of fever, chills, weakness, palpitation, and sinus congestion.

Conclusion:

Lung cancer can be a life-threatening condition. In spite of conventional treatments like radiation therapy or chemotherapy, it is difficult to kill cancer cells. Immunotherapy can be useful in such conditions. Immunotherapeutic drugs can modulate the immune system and can help to kill cancer cells.