Immunotherapy in Small Cell Lung Cancer Treatment: a Promising Headway for Future Perspective.

ABSTRACT

OPINION STATEMENT Despite advancements in clinical research, both prognosis and treatment for SCLC patients are still in the nascent stage. SCLC is a fatal disease with high tumor mutational burden and is strongly associated with exposure to tobacco. This leads to the development of potential neo-antigens, inhibition of immune responses, and development of paraneoplastic disorders. Surgery, radiation, and chemotherapy are widely accepted treatments for cancer globally, and most recently, immunotherapy has now become the "fourth pillar" of SCLC treatment. Various immune checkpoint pathways regulate the activation of T cells at multiple stages during an immune response. T cell checkpoint inhibitors such as anti-PD1 (pembrolizumab, nivolumab), anti-PDL1, and anti-CTLA-4 (tremelimumab, ipilimumab) have potential to show anti-cancer activity along with the promise to prolong survival in patients with SCLC. Treatment with the CTLA-4-specific antibodies can restore the immune response by increasing the accumulation and survival of T-cells whereas monoclonal antibodies block either PD-1 or its ligands that prevent downregulation of effector T-cell, which enables the T-cells to mediate the death of tumor cells. Furthermore, monoclonal antibody in combination with chemotherapy has attained quite a focus to enhance the survival of SCLC patients. Apart from this, various immunotherapeutic approaches have been evaluated in the clinical trials for SCLC patients such as TLR9 agonist, anti-CD47, anti-ganglioside therapy, and anti-Notch signaling. The current review focuses on the rationale as well as on the clinical studies of immunotherapy in SCLC along with the clinical end results of certain immunotherapeutic agents and novel therapeutic combinations in SCLC patients.