Innate immune function during antineoplastic treatment is associated with 12-months survival in non-small cell lung cancer

Abstract

IntroductionThe immune system has proven to be a key player in the progression as well as containment of cancer with new treatment strategies based on immunotherapy targeting this interaction. Assessing immune function could reveal critical information about the immune response to therapeutic interventions, revealing predictive biomarkers for tailored care and precision medicine.MethodsWe investigated immune function in 37 patients with inoperable non-small cell lung cancer (NSCLC) undergoing treatment with PD-L1 immune checkpoint inhibitor (ICI), chemotherapy (CT) or chemo-radiotherapy (CT/RT). Blood samples before (day 0) and during therapy (day 7, 21 and 80) were investigated by a standardized immunoassay, TruCulture®.ResultsOutcomes revealed a developing innate immune response induced by both immunotherapy and chemotherapy. NSCLC-patients displayed evidence of chronic innate immune activation and exhaustion prior to treatment. This pattern was particularly pronounced during treatment in patients dying within 12-months follow-up. Compared to treatment with CT, ICI demonstrated a higher ex vivo-stimulated release of proinflammatory cytokines.DiscussionThese preliminary findings may pave the way for tailored treatment and immune-monitoring.

The impact of concurrent bacterial lung infection on immunotherapy in patients with non-small cell lung cancer: a retrospective cohort study

“…This suggests that the increase in exhausted CD8+T lymphocytes in the BLI microenvironment may be closely related to the occurrence and progression of tumors. Our study found that NSCLC patients with concurrent BLI had better ORR and PFS after immunotherapy, consistent with previous studies (Cortellini et al, 2021a;Ryssel et al, 2022;Zhang et al, (2022)). The mechanism for this phenomenon may be that the characteristic tumor micro-environment of BLI is more suitable for PD-1/PD-L1 pathway inhibitors to work, thereby reversing T lymphocyte exhaustion in tumor tissues, restoring T lymphocyte activity, and better exerting anti-tumor effects.…”

Clinical implications of innate immune exhaustion in cystic fibrosis

“…However, the sample size was too small to draw firm conclusions. It has previously been described that high ex vivo unstimulated cytokine release and low stimulated cytokine release may reflect exhaustion [14]. Thus, our data indicate that the immune system in CF might be exhausted or impaired after long-term persistent infection and inflammation [24], similar to what is seen in other types of inflammatory diseases [25].…”

“…This might explain why studies of the CF immune response have found varying and at times inconsistent tendencies [9,12]. A new standardized immune assay (TruCulture -Myriad RBM, Austin, TX, US) has been developed and tested as a predictive and diagnostic tool to link systemic immune responses to clinical parameters in several clinical cohorts, including people undergoing surgery, people with cancer and people with neuroborreliosis [13][14][15][16]. TruCulture estimates unstimulated and stimulated cytokine release to TLR agonists in whole blood using test tubes containing standardized concentrations of different agonists.…”

Whole blood stimulation as a tool for studying the human immune system

“…Combining whole blood stimulation with longitudinal sampling of patients has been used to monitor changes in responsiveness over time with regard to disease progression and treatment‐induced effects. For example, longitudinal sampling before and during treatment was performed to study innate immune function during different cancer treatments [63] and combinational antiretroviral therapy in HIV [64]. Further, longitudinally sampling COVID‐19 patients from admission to the hospital until dismissal (or death) revealed that lower release of IL‐1β upon LPS as well as IL‐12 and IL‐17A upon R848 stimulation at admission were associated with more severe disease at peak severity [65].…”