Lung Cancer Immune Checkpoint Configuration for Therapeutic Use

Da Ma^*
*Correspondence: Da Ma, Department of Pulmonology, University of Miami School of Medicine, Miami, Florida, USA, Email:

Keywords

Lung Cancer • Immunotherapy • Immunological checkpoints

Introduction

In order to test various Immune Checkpoint Inhibitors (ICIs) for its management, it is essential to comprehend the biological and clinical characteristics of lung cancer. Lung cancer has a high tumor mutational burden, or number of genetic changes, which makes it more immunogenic and prone to ICI-response. By acting as coinhibitory factors, these ICIs are primarily responsible for reducing antigen-specific immune responses. The most extensively researched ICI targets for lung cancer are Programmed Death protein 1 (PD-1), its ligand, Programmed cell Death ligand 1 (PD-L1) and Cytotoxic T-Lymphocyte-Associated Antigen 4 (CTLA-4). CTLA-4 is expressed on the surface of T cells, facilitating the initial activation of T cells in lymph nodes [1]. After that, it binds to its CD80/CD86 receptors on antigen-presenting cells and sends T cells inhibitory signals. When PD-1 on T cells interacts with PD-L1 on antigen-presenting cells, T cells are inhibited. In patients with SCLC, the ICIs have also been tested as a single therapy.

Description

Pembrolizumab monotherapy was given to a group of SCLC patients as a second-line treatment, with PFS of 1.4 and OS of 9.6 months. When looking at the data from the past, this did not provide any additional advantages. Therefore, in SCLC patients, pembrolizumab immunotherapy does not improve PFS or OS. In one particular study, durvalumab was given to patients who had been treated for SCLC as a second-line drug as a single treatment. The disease control rate was 14.3%, while the ORR was 9.5%. PFS and OS lasted on average 1.5 and 4.8 months, respectively [2]. The toxicity profile did not significantly change, but there was a significant improvement in efficacy. Patients with SCLC who relapsed after receiving platinum-based chemotherapy were the subject of a study. The outcomes of these patients, who received nivolumab monotherapy, were compared to those of a group receiving chemotherapy. It was discovered that the ORR in the lumab group was 13.7%. Nivolumab monotherapy was approved for use in SCLC on the basis of this [3].

Atezolizumab has been tested as a single treatment for NSCLC, but little research has been done on it for SCLC. Atezolizumab's safety and effectiveness in SCLC patients are currently being tested in a clinical trial. The ORR was 19.5% and the OS rate was 48 percent, according to the data that are currently available for the same. Ipilimumab, an anti-CTLA-4 antibody is frequently used in combination therapy with other ICIs. T cell-mediated immunity and anticancer effects are activated when these checkpoints are inhibited [4]. For NSCLC, nivolumab, pembrolizumab, atezolizumab, durvalumab and cemiplimab are currently approved while durvalumab is currently approved for SCLC. Other molecules on these targets, as well as newer ICI targets, are being discovered in addition to PD-1 and CTLA-4. These include the T cell immunoreceptor with Ig and immunoreceptor tyrosine-based inhibitory motif domains, the lymphocyte activation gene 3, the V-domain immunoglobulin-containing suppressor of T cell activation and the human endogenous retrovirus-H long terminal repeatassociating protein 2 [5].

Conclusion

In the treatment of lung cancer, ICIs have been shown to have significant therapeutic value and clinical justification as a component of immunotherapy. Only a few checkpoints and a few ICIs have been the subject of research up to this point. ICIs currently target the PD-1 and CTLA4 checkpoints in clinical settings. After more research, drugs that target various other immune checkpoints may be developed. These novel checkpoints mentioned above may be helpful in the treatment of lung cancer. Other checkpoints have been identified, as previously mentioned, but the agents that act on them have not yet been utilized in clinical settings. In order to incorporate these agents into therapy, extensive strategic research is required. The role of immunological checkpoints in the progression of cancer is also discussed, as is the significance of ICIs in the management of NSCLC/SCLC. Lung cancer, the most common type, accounts for the majority of cancer-related deaths. Despite being treated with a variety of chemotherapeutic regimens at the moment, no satisfactory results have been achieved. Immunotherapy is a recent option for enhancing various outcomes related to cancer. Up until now, immunotherapy has been viewed as an additional treatment, obscuring its actual effectiveness.

Acknowledgement

None.

Conflict of Interest

None.

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