Prognostic Factors and Biomarkers of Responses to Immune Checkpoint Inhibitors in Lung Cancer

Abstract

Manipulation of the immune response is a game changer in lung cancer treatment, revolutionizing management. PD1 and CTLA4 are dynamically expressed on different T cell subsets that can either disrupt or sustain tumor growth. Monoclonal antibodies (MoAbs) against PD1/PDL1 and CTLA4 have shown that inhibitory signals can be impaired, blocking T cell activation and function. MoAbs, used as both single-agents or in combination with standard therapy for the treatment of advanced non-small cell lung cancer (NSCLC), have exhibited advantages in terms of overall survival and response rate; nivolumab, pembrolizumab, atezolizumab and more recently, durvalumab, have already been approved for lung cancer treatment and more compounds are in the pipeline. A better understanding of signaling elicited by these antibodies on T cell subsets, as well as identification of biological determinants of sensitivity, resistance and correlates of efficacy, will help to define the mechanisms of antitumor responses. In addition, the relevance of T regulatory cells (Treg) involved in immune responses in cancer is attracting increasing interest. A major challenge for future research is to understand why a durable response to immune checkpoint inhibitors (ICIs) occurs only in subsets of patients and the mechanisms of resistance after an initial response. This review will explore current understanding and future direction of research on ICI treatment in lung cancer and the impact of tumor immune microenvironment n influencing clinical responses.

COVID-19 and the elderly: insights into pathogenesis and clinical decision-making

“…Though vaccines do not succeed in eradicating influenza, their positive effect, in modulating infection and preventing complications and sequelae including pneumonia, other bacterial infections, and even death, must be acknowledged [72]. Unfortunately, the effectiveness of vaccines among older people against influenza-like illness has been reported to be reduced in comparison with younger subjects, reflecting an impairment of both effector memory T cells and efficient B cells [64,73,74]. Questions upon the impact of these features on the COVID-19 course in elderly patients remain.…”

Efficacy of Anti-PD1/PD-L1 Therapy (IO) in KRAS Mutant Non-small Cell Lung Cancer Patients: A Retrospective Analysis

“…Most recently, the introduction of immunotherapy represented a paradigm shift in the treatment of NSCLC without any clinically actionable mutations (5). Of note, not all patients benefit from immunotherapy, but neither PD-L1 nor TMB proved to be an optimal predictor of IO efficacy (6)(7)(8). For this reason, the identification of other potential biomarkers that could predict clinical response or resistance to immunotherapy is crucial.…”

Intratumoral versus Circulating Lymphoid Cells as Predictive Biomarkers in Lung Cancer Patients Treated with Immune Checkpoint Inhibitors: Is the Easiest Path the Best One?

“…All these components create, by different mechanisms, an immunosuppressive state that allows tumor cells to remain hidden from the immune system and to continue their growth. Some of these immune-escape mechanisms are an inappropriate presentation of tumor antigens, the secretion of inhibitory cytokines and chemokines, tumor mutations to achieve molecules unrecognizable by the immune system, and the attraction and recruitment of inhibitory cells [13].…”