Lung cancer immunotherapy: progress, pitfalls, and promises

Abstract

Lung cancer is the primary cause of mortality in the United States and around the globe. Therapeutic options for lung cancer treatment include surgery, radiation therapy, chemotherapy, and targeted drug therapy. Medical management is often associated with the development of treatment resistance leading to relapse. Immunotherapy is profoundly altering the approach to cancer treatment owing to its tolerable safety profile, sustained therapeutic response due to immunological memory generation, and effectiveness across a broad patient population. Different tumor-specific vaccination strategies are gaining ground in the treatment of lung cancer. Recent advances in adoptive cell therapy (CAR T, TCR, TIL), the associated clinical trials on lung cancer, and associated hurdles are discussed in this review. Recent trials on lung cancer patients (without a targetable oncogenic driver alteration) reveal significant and sustained responses when treated with programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) checkpoint blockade immunotherapies. Accumulating evidence indicates that a loss of effective anti-tumor immunity is associated with lung tumor evolution. Therapeutic cancer vaccines combined with immune checkpoint inhibitors (ICI) can achieve better therapeutic effects. To this end, the present article encompasses a detailed overview of the recent developments in the immunotherapeutic landscape in targeting small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Additionally, the review also explores the implication of nanomedicine in lung cancer immunotherapy as well as the combinatorial application of traditional therapy along with immunotherapy regimens. Finally, ongoing clinical trials, significant obstacles, and the future outlook of this treatment strategy are also highlighted to boost further research in the field.

A Predictive Model for Evaluating Efficacy of Immunotherapy in Non-small-cell Lung Cancer Patients

“…TMB, as a predictive factor for immune therapy, still needs to be supplemented by other valid forecasting information. As we have listed above, the response rate to immunotherapy in patients with high levels of TMB is still low [14]. In addition, the results of multivariable Cox regression analysis showed that the TMB was not an independent predicator.…”

“…Besides, the guidelines give treatment suggestion according to the level of PD-L1 expression and TMB. However, some patients with high PD-L1 expression or a high level of TMB did not response to ICIs [14]. Accordingly, there is an urgent need to nd out predicative factors with more accuracy.…”

“…In addition, NSCLC patients with high PD-L1 expression or a high level of TMB have an effective response to ICIs generally. However, there are still some patients showing no response to ICIs, even with high PD-L1 expression or a high level of TMB [14]. Accordingly, it is important to nd exact and reliable predicting factors to assess the effect of ICIs.…”

The emerging nanomedicine-based technology for non-small cell lung cancer immunotherapy: how far are we from an effective treatment

“…The infiltration levels of both CD8+ and CD4+ T cells were augmented, and NK cells were activated, concomitant with the reduction of myeloid-derived suppressor cells (MDSCs) and regulatory T cells expressing the Foxp3 transcription factor (Foxp3+ Tregs), known for their role in immune tolerance ( 69 ). Numerous studies are still underway to investigate the potential of immunomodulatory nanomedicine in lung cancer immunotherapy, and we anticipate a surge in their applications in the near future ( 70 – 72 ).…”

Survival of small-cell lung cancer patients after surgery: A single-center retrospective cohort study

“…However, with advances in diagnostic and surgical technologies, many researchers have begun challenging the current view of surgery in treating SCLC and have attempted to expand the surgical indications for SCLC. 5–10…”