Immunotherapeutic Advances for NSCLC

Abstract

Immunotherapy with antibodies against PD-1 or PD-L1, either alone or in combination with chemotherapy, has revolutionized treatment paradigms of non-small cell lung cancer (NSCLC) patients without oncogenic driver alterations. These agents, namely immune checkpoint inhibitors (ICIs), have also widely demonstrated a remarkable efficacy in locally advanced as well as in early-stage NSCLC. Assessment of tumor PD-L1 expression by immunohistochemistry has entered into routine clinical practice to select patients for immunotherapy, even though its predictive role has long been debated. Despite improved survival outcomes over standard chemotherapy, treatment with ICIs is associated with initial low response rate, with a significant proportion of patients not responding to these agents. Hence, novel appealing predictive biomarkers, such as those related to tumor cell signaling pathways, metabolism or the tumor microenvironment, have emerged as potentially useful to select those patients most likely to benefit from immunotherapy. Moreover, most patients ultimately develop acquired resistance to ICI treatment over time and novel therapeutic strategies are urgently needed to overcome or delay resistance. Herein, we provide an overview on recent advances in immunotherapy in NSCLC, focusing on updated results from studies on ICIs in different disease settings and at different lines of treatment. We further describe currently emerging predictive biomarkers, beyond PD-L1, to optimize patient selection and novel strategies to improve clinical outcomes.

A Self-Assembly ICG Nanoparticle Potentiating Targeted Photothermal and Photodynamic Therapy in NSCLC

“…Although the introduction of targeted therapies and immunotherapy have greatly evolved the landscape of treatment for patients with nonsmall cell lung cancer (NSCLC), NSCLC is still the first leading cause of cancer-related death. , Improved therapeutic efficacy and survival benefits are still absent in many patients . More treatment options for nonresponder patients are urgently needed .…”

“…2,3 Improved therapeutic efficacy and survival benefits are still absent in many patients. 4 More treatment options for nonresponder patients are urgently needed. 5 Phototherapy, which absorbs light energy to generate heat as photothermal therapy (PTT) or reactive oxygen species (ROS) as photodynamic therapy (PDT) to induce cell death, are noninvasive and selective treatment strategies and appear as promising alternative treatments since they do not compromise other treatment options such as chemotherapy or radiotherapy.…”

Cost‐effectiveness of first‐line versus second‐line use of domestic anti‐PD‐1 antibody sintilimab in Chinese patients with advanced or metastatic squamous non‐small cell lung cancer

“… 5 Programmed cell death protein‐1/programmed cell death ligand‐1 (PD‐1/L1) inhibitor immunotherapies have shown a remarkable performance in treating driver‐negative advanced or metastatic sqNSCLC and they have now become the mainstay therapies in this patient group. 6 …”

“…5 Programmed cell death protein-1/programmed cell death ligand-1 (PD-1/ L1) inhibitor immunotherapies have shown a remarkable performance in treating driver-negative advanced or metastatic sqNSCLC and they have now become the mainstay therapies in this patient group. 6 Between 2018 and 2019, the Chinese National Medical Products Administration successively approved three imported anti-PD-1/L1 drugs (pembrolizumab, atezolizumab and nivolumab) for advanced or metastatic sqNS-CLC. 7 Despite the compelling clinical evidences showing great efficacy of these imported anticancer drugs, the prohibitively high costs make these drugs unaffordable for the majority of patients.…”

Occurrence of hyperprogressive disease following administration of immune checkpoint inhibitors in lung squamous cell carcinoma: A case report

“…Therefore, it can find and attack cancer cells at several important nodes. Solid tumors can induce programmed death-ligand 1 (PD-L1) expression, targeting programmed cell death 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) pathways in tumor therapy to avoid the escape from the immune response (3). PD-1 is a key mediator in the induction of T cell exhaustion in chronic inflammation or patients with cancer (4).…”