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Background: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment landscape for non-small cell lung cancer (NSCLC). The variability in patient responses necessitates a blood-based, multi-cohort gene signature to predict ICI response in NSCLC. Methods: We performed transcriptomic profiling of peripheral blood mononuclear cell (PBMC) and buffy coat (BC) samples from three independent cohorts of NSCLC patients treated with ICIs: a retrospective cohort (PMBCR, n = 59), a retrospective validation cohort (BC, n = 44), and a prospective validation cohort (PBMCP, n = 42). We identified a 5-gene signature (UQCRB, NDUFA3, CDKN2D, FMNL1-DT, and APOL3) predictive of ICI response and validated its clinical utility in the prospective PBMCP cohort. Response was evaluated using RECIST criteria, and patients were followed up for progression-free survival (PFS) and overall survival (OS). Results: In the prospective PBMCP cohort, the 5-gene signature demonstrated high accuracy in stratifying patients into responders and non-responders (AUC = 0.89, 95% CI: 0.80–0.99). Predicted responders exhibited significantly longer PFS compared to predicted non-responders (median: 13.8 months vs. 4.2 months, HR = 0.21, 95% CI: 0.07–0.58, p = 0.005). Conclusion: Our study confirms a 5-gene signature as a key biomarker for ICI response in NSCLC, enhancing treatment precision. [ABSTRACT FROM AUTHOR]

Background: Immune Checkpoint Inhibitors (ICIs) lead to durable response and a significant increase in long-term survival in patients with advanced malignant melanoma (MM) and Non-Small Cell Lung Cancer (NSCLC). The identification of serum cytokines that can predict their activity and efficacy, and their sex interaction, could improve treatment personalization. Methods: In this prospective study, we enrolled immunotherapy-naïve patients affected by advanced MM and NSCLC treated with ICIs. The primary endpoint was to dissect the potential sex correlations between serum cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, GM-CSF, MCP-1, TNF-ɑ, IP-10, VEGF, sPD-L1) and the objective response rate (ORR). Secondly, we analyzed biomarker changes during treatment related to ORR, disease control rate (DCR), progression free survival (PFS) and overall survival (OS). Blood samples, collected at baseline and during treatment until disease progression (PD) or up to 2 years, were analyzed using Luminex xMAP or ELLA technologies. Results: Serum samples from 161 patients (98 males/63 females; 92 MM/69 NSCLC) were analyzed for treatment response. At baseline, IL-6 was significantly lower in females (F) versus males (M); lower levels of IL-4 in F and of IL-6 in both sexes significantly correlated with a better ORR, while higher IL-4 and TNF-ɑ values were predictive of a lower ORR in F versus M. One hundred and sixty-five patients were evaluable for survival analysis: at multiple Cox regression, an increased risk of PD was observed in F with higher baseline values of IL-4, sPD-L1 and IL-10, while higher IL-6 was a negative predictor in males. In males, higher levels of GM-CSF predict a longer survival, whereas higher IL-1β predicts a shorter survival. Regardless of sex, high baseline IL-8 values were associated with an increased risk of both PD and death, and high IL-6 levels only with shorter OS. Conclusions: Serum IL-1β, IL-4, IL-6, IL-10, GM-CSF, TNF-ɑ, and sPD-L1 had a significant sex-related predictive impact on ORR, PFS and OS in melanoma and NSCLC patients treated with ICIs. These results will potentially pave the way for new ICI combinations, designed according to baseline and early changes of these cytokines and stratified by sex. [ABSTRACT FROM AUTHOR]

Objectives: ICIs have become the standard treatment for advanced NSCLC patients. Currently, PD-L1 is the most widely useful biomarker to predict ICI efficacy, but the sensitivity and specificity are limited. Therefore, the useful predictive biomarkers of ICI efficacy is urgently needed. BMI is an internationally used measure of body health. Obesity may affect ICI efficacy by changing T cell functions. This meta-analysis aimed to clarify the relationship between BMI and survival outcomes of NSCLC patients treated with ICIs. Methods: A systematic review was conducted to identify studies that assessed the association between BMI and survival outcomes in patients treated with ICIs. OS was the primary endpoint, and PFS was the secondary endpoint. Random-effect models or fixed-effect models were utilized to combine study effects according to the Cochran Q and I2 tests. Results: Nine studies, including 4602 NSCLC patients treated with ICIs, that met the inclusion criteria were selected for this meta-analysis. There was no significant difference in PFS (HR 0.885; 95% CI 0.777–1.009, p = 0.068) or OS (HR 0.947; 95% CI 0.789–1.137, p = 0.560) between the low BMI group and the high BMI group. However, in the subgroup analysis, compared with normal-weight patients, overweight and obese patients achieved prolonged PFS (HR 0.862; 95% CI 0.760–0.978, p = 0.021) and OS (HR 0.818; 95% CI 0.741–0.902, p<0.0001). Conclusion: Overweight and obese NSCLC patients tend to achieve prolonged survival time with ICI regimens. Further prospective studies are needed to strengthen the association between ICI outcomes and BMI levels. [ABSTRACT FROM AUTHOR]

Background: Non-Small Cell Lung Cancer (NSCLC) is one of the most prevalent malignancies globally, accounting for 85% of lung cancer cases. The rapid advancements in immunotherapy have significantly improved the prognosis of NSCLC patients. Methods: This article provides a comprehensive review of the clinical applications and latest research on commonly used immune checkpoint inhibitors as well as emerging immune checkpoint inhibitors and agonists in NSCLC treatment, providing valuable clinical guidance. Results: Immune checkpoint inhibitors, including PD-1/PD-L1 inhibitors and CTLA-4 inhibitors, have been widely utilized in NSCLC treatment, leading to substantial increases in patient survival and improvements in quality of life. However, challenges persist in terms of tumor complexity, interindividual variability, drug resistance, and adverse reactions. The emergence of novel immune checkpoints, such as LAG-3, TIM-3, OX-40, and ICOS, opens up new research directions to address these issues. Conclusion: Immune checkpoint inhibitors play a crucial role in the treatment of NSCLC, and the investigation of emerging immune checkpoint inhibitors and agonists presents promising therapeutic opportunities. A comprehensive evaluation of the efficacy and safety of these drugs contributes to the development of personalized treatments, ultimately enhancing treatment outcomes and prognosis for NSCLC patients. [ABSTRACT FROM AUTHOR]

Background: Anti-angiogenic drugs increase anti-tumor efficacy of immune checkpoint inhibitors (ICIs). However, the optimal dose of anti-angiogenic drugs remains unclear. Methods: We retrospectively analyzed efficacy and safety data from patients diagnosed with advanced or metastatic non-small cell lung cancer (NSCLC) that received PD-1 blockade with low-doses of anlotinib, a highly selective receptor tyrosine kinase inhibitor mainly targeting vascular endothelial growth factor receptors, as second or later line therapy. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), overall response rate (ORR), disease control rate (DCR), and safety profile. Univariate and multivariate analyses were used to identify prognostic factors. Results: A total of 40 eligible patients were included. The median PFS was 11.4 months. The median OS of the entire cohort was 27.0 months. ORR was achieved in 16 patients (40.0%) and DCR was maintained in 33 patients (82.5%). The overall incidence of adverse events (AEs) was 52.5%, and the most common all grade AE was gastrointestinal reactions, which occurred in four patients (10.0%). Treatment-related grade 3/4 toxicity was observed in one patient (2.5%). Conclusions Low-dose anlotinib may be an effective and well-tolerated anti-angiogenesis partner for combination therapy with ICIs in second-line and later settings for advanced NSCLC. [ABSTRACT FROM AUTHOR]

Several types of immune checkpoint inhibitors (ICIs) have been reported to occasionally cause Vogt-Koyanagi-Harada disease (VKHD)-like uveitis. Among the ICIs, the anti-programmed death ligand-1 (PD-L1) antibody is reported to cause fewer immune-related adverse events (irAEs). We report a case of VKHD-like uveitis that developed after anti-PD-L1 antibody treatment for non-small cell lung cancer (NSCLC). A 76-year-old woman suffered from an acute visual reduction in both eyes. She had been treated with atezolizumab, an anti-PD-L1 antibody, for NSCLC for 17 months. Ophthalmologic examinations led to a diagnosis of severe VKHD-like uveitis, and one of the irAEs was suspected. Discontinuation of atezolizumab and systemic steroid therapy led to the resolution of the findings within two months. This is the first report of VKHD-like uveitis that developed during the treatment by anti-PD-L1 antibody. Our case indicates that VKHD-like uveitis may be induced after a long-time use of anti-PD-L1 antibody. [ABSTRACT FROM AUTHOR]

Background : Lung cancer has the highest morbidity and mortality rate among types of malignant tumors, and as such, research into prolonging the survival time of patients is vital. The emergence of immune checkpoint inhibitors (ICIs) has greatly improved the survival of patients with non-small cell lung cancer (NSCLC), however, the lack of effective biomarkers to predict the prognosis of immunotherapy has made it difficult to maximize the benefits. T cell receptor (TCR) is one of the most important components for recognizing tumor cells, and with this study we aim to clarify the relationship between TCR coexpression and the prognosis of NSCLC patients receiving immunotherapy. Methods : Univariate COX regression, logistics regression, and KM survival analysis were used to evaluate the relationship between TCR coexpression and the prognosis of immunotherapy. Additionally, CIBERSORT, Gene Set Enrichment Analysis (GSEA), and single-sample GSEA (ssGSEA) algorithms were used to evaluate the tumor immune microenvironment (TIME) of NSCLC patients. Results : Univariate Cox regression analysis showed that the TCR coexpression signature can be used as a clinical prognostic indicator for NSCLC patients receiving immunotherapy (p = 0.0205). In addition, those in the NSCLC group with a high TCR coexpression signature had significantly improved progression-free survival (PFS) (p = 0.014). In the ICI treatment cohort (GSE35640). In addition, there was a high infiltration of CD8+T cells, activated memory CD4+T cells, and M1 macrophages in the TIME of those with a high TCR coexpression signature. The results of pathway enrichment analysis showed that patients with a high TCR coexpression signature had significantly activated signal pathways such as lymphocyte proliferation and activation, chemokine binding, and inflammatory cytokine production. Also, we found that patients with a high TCR coexpression signature had an elevated T cell inflammation gene expression profile (GEP). Conclusion : We show that the TCR coexpression signature may be useful as a new biomarker for the prognosis of NSCLC patients undergoing immunotherapy, with high signatures indicating better treatment response. Additionally, we found that patients with a high TCR coexpression signature had tumor immune microenvironments with beneficial anti-tumor characteristics. [ABSTRACT FROM AUTHOR]

Translational research on immune checkpoint inhibitors (ICIs) has been underway. However, in the unselected population, only a few patients benefit from ICIs. Therefore, screening predictive markers of ICI efficacy has become the current focus of attention. We collected mutation and clinical data from an ICI-treated non-small cell lung cancer (NSCLC) cohort. Then, a univariate Cox regression model was used to analyze the relationship between tumor necrosis factor α signaling mutated (TNFα-MT) and the prognosis of immunotherapy for NSCLC. We retrospectively collected 36 NSCLC patients (local-cohort) from the Zhujiang Hospital of Southern Medical University and performed whole-exome sequencing (WES). The expression and mutation data of The Cancer Genome Atlas (TCGA)-NSCLC cohort were used to explore the association between TNFα-MT and the immune microenvironment. A local cohort was used to validate the association between TNFα-MT and immunogenicity. TNFα-MT was associated with significantly prolonged overall survival (OS) in NSCLC patients after receiving immunotherapy. Additionally, TNFα-MT is related to high immunogenicity (tumor mutational burden, neoantigen load, and DNA damage response signaling mutations) and enrichment of infiltrating immune cells. These results suggest that TNFα-MT may serve as a potential clinical biomarker for NSCLC patients receiving ICIs. [ABSTRACT FROM AUTHOR]

Purpose: Although predictive markers of immune checkpoint inhibitor (ICI)-based treatments have been extensively studied, with the exception of programmed death ligand 1 (PD-L1), most are not widely used in the clinic due to poor effects or defective practicability. The aim of this study was to identify those patients with high baseline serum cholesterol who benefit from ICI-based treatments. Patients and Methods: Patients with advanced non-small cell lung cancer (NSCLC) treated at Ningbo Medical Center, Li Huili Hospital between August 2017 and December 2019 were enrolled in this retrospective study. The Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) were used to evaluate the efficacy of the ICI-based treatment. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan–Meier survival curves and compared using the log rank test. Univariate and multivariate analyses were conducted using the logistic regression analysis and Cox proportional hazards model. A receiver operating characteristic curve was created, and the area under the curve (AUC) was calculated to compare the predictive value of baseline serum cholesterol with PD-L1 expression for patient response to ICI-based treatment. Results: In our cohort of 169 NSCLC patients, the objective response rate (ORR) and disease control rate (DCR) of the treatment were significantly higher in patients with hypercholesterolemia (> 5.18 mmol/L) than in those with hypocholesterolemia (ORR: 33.67% vs 14.08%, P=0.004; DCR: 68.37% vs 42.25%, P=0.001). The median PFS was 7.9 months in the hypercholesterolemia group, significantly longer than in the hypocholesterolemia group (4.4 months, 95% CI: 4.620– 7.380, P< 0.001). The median OS in the two groups were 11 months and 8 months, with 95% CIs of 8.980– 10.420 (P< 0.001). The AUC for the baseline level of cholesterol was 0.706 (P< 0.001), while it was 0.643 (P=0.001) for PD-L1 expression. Conclusion: The baseline serum cholesterol level is predictive of a clinical benefit for advanced NSCLC patients who undergo ICI-based treatment, and hence it is a promising prognostic indicator for ICI-based treatment of NSCLC. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed at investigating the value of applying positron emission tomography (PET) to early predict the effect of immune checkpoint inhibitors (ICIs) in malignant tumors. Methods: Electronic databases MEDLINE/PubMed, EMBASE, and Cochrane Library were searched to identify relevant trials. The primary endpoints were progression-free survival (PFS) and overall survival (OS). The results were analyzed utilizing SPSS 19.0 statistical software. Subgroup analyses were implemented based on primary tumors, study designs, continents, type of ICIs, evaluation index of PET, and evaluated PET timing. Results: Fifteen studies incorporating 664 individuals were eligible. Compared with PET nonresponse group, PET response group displayed a significantly prolonged PFS (HR 0.27, 95% CI [0.16, 0.44]; P < 0.001) and OS (HR 0.56, 95% CI [0.48, 0.65]; P < 0.001). Analogical outcomes were obtained in subgroup analyses of PFS in non-small cell lung cancer, prospective, America, ipilimumab, nivolumab/pembrolizumab combined ipilimumab, PET Response Criteria in Solid Tumors (PERCIST), baseline PET and early PET timing arms without heterogeneity; so did OS in melanoma, retrospective, Europe, America, ipilimumab, nivolumab/pembrolizumab, PERCIST, baseline metabolic tissue volume, baseline standard uptake value, and baseline total lesion glycolysis, baseline PET timing, early PET timing and late PET timing arms. Conclusion: Our study demonstrated that PET was a promising approach to early predict the prognosis of ICIs for malignancies. [ABSTRACT FROM AUTHOR]

Since 2015, immunotherapies, especially immune checkpoint inhibitors (ICIs), have made great breakthroughs in non-small-cell lung cancer (NSCLC). Among them, nivolumab, pembrolizumab and atezolizumab have been granted US Food and Drug Administration approval for NSCLC. It is imperative to combine ICIs with chemotherapy, radiotherapy, antivascular therapy and targeted therapy. But in the bright future, there are two problems. One is how to use biomarkers to select the beneficiaries. The other is how to achieve a balance between drug effectiveness and safety. There are now seven drugs targeting the programmed death-1/programmed death ligand-1 (PD-1/PD-L1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) pathways that have been or are expected to enter clinical treatment. This review focuses on these drugs and summarizes clinical trials that have been reported or that ongoing ones have already entered the recruiting state. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC) is one of the main malignant tumors with high mortality and short survival time. Immunotherapy has become the standard treatment for advanced NSCLC, but it has the problems of drug resistance and low response rate. Therefore, obtaining effective biomarkers to predict and enhance immune checkpoint inhibitors (ICIs) efficacy in NSCLC is important. Sphingolipid metabolism is recently found to be closely involved in tumor immunotherapy. CERS4, an important sphingolipid metabolizing enzyme, is positively correlated with the efficacy of anti-PD-1 therapy for NSCLC. Upregulation of CERS4 expression could improve the efficacy of anti-PD-1 therapy for NSCLC. High expression of CERS4 could downregulate the expression of Rhob in tumor. Significantly, the ratio of CD4+/CD8+ T cell increased and the ratio of Tim-3+/CD8+ T cell decreased in spleen and peripheral blood cells. When Rhob was knocked out, the efficacy of PD-1 mAb treatment increased, and the frequency of Tim-3+ CD8+ T cell decreased. This finding further confirmed the role of sphingolipid metabolites in regulating the immunotherapeutic function of NSCLC. These metabolites may improve the efficacy of PD-1 mAb in NSCLC by regulating the CERS4/Rhob/Tim-3 axis. Overall, this study provided a potential and effective target for predicting and improving the efficacy of ICIs for NSCLC. It also provided a new perspective for the study on the mechanisms of ICIs resistance for NSCLC. [Display omitted] [ABSTRACT FROM AUTHOR]

Programmed death-ligand 1 (PD-L1) has been widely used in immunotherapy evaluation of patients with non-small cell lung cancer (NSCLC). However, the effect is not particularly ideal, and the association between PD-L1 and genetic alterations requires more exploration. Here, we performed targeted next-generation sequencing and PD-L1 immunohistochemistry (IHC) testing for PD-L1 expression on both tumor cells (TCs) and tumor-infiltrating immune cells (ICs) in 1549 patients. Our studies showed that surgical method of resection was positively correlated with IC+, and a low tumor mutation burden (TMB) was negatively correlated with TC+. Furthermore, we found that EGFR was mutually exclusive with both ALK and STK11. In addition, the features between PD-L1 expression status and genomic alterations were characterized. These results suggest that clinical characteristics and molecular phenotypes are associated with PD-L1 expression signatures, which may provide novel insights for improving the efficiency of immune checkpoint inhibitors (ICIs) in immunotherapy. • Genomic landscape and PD-L1 status of lung cancer tissues from 1549 patients • Identification of the correlation between genetic alterations and PD-L1 expression on TCs and ICs • Characterization of the correlation between clinical characteristics and PD-L1 expression on both TCs and ICs • These findings may provide valuable information for accurately focusing on the beneficiaries of ICIs during immunotherapy [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) have been an encouraging treatment method in non-small cell lung cancer (NSCLC). However, bone and liver metastases are considered to restrain immunotherapy efficacy. Since serum alkaline phosphatase (ALP) is associated with bone and liver metastases, it was investigated whether serum ALP could be a novel biomarker to predict the efficacy of ICIs treatment. In the present study, 143 patients with NSCLC receiving ICIs treatment were retrospectively analyzed. The objective response rate (ORR) was compared between the ALP high and low groups, bone metastasis and non-bone metastasis groups, and liver metastasis or non-liver metastasis groups. The associations between clinical characteristics, including ALP level, bone or liver metastasis and median progression-free survival (mPFS) time were analyzed by univariate and multivariate Cox regression analysis. It was found that bone metastasis was associated with a lower ORR (24 vs. 43%; P<0.05) and shorter mPFS (10.2 vs. 17.3 months; P=0.010) in patients with NSCLC receiving ICIs. Liver metastasis was associated with lower ORR (22 vs. 38%; P<0.05), but not with mPFS (P=0.119). The ALP level was higher in patients with bone or liver metastasis than in those without (119.6 or 103.6 vs. 83.3 U/l, respectively; P<0.05). Higher ALP levels were also associated with bone or liver metastasis, lower ORR (20 vs. 39%; P<0.05) and shorter mPFS (8.5 vs. 15.4 months; P=0.009). Cox regression analysis demonstrated that ALP was an independent prognostic indicator of mPFS (hazard ratio, 1.856; 95% confidence interval, 1.030-3.343; P=0.040). In conclusion, pretreatment levels of serum ALP might be a predictive indicator of clinical outcome in patients with NSCLC after ICIs treatment. [ABSTRACT FROM AUTHOR]

• TKIs and ICIs are pivotal for the treatment of advanced NSCLC. • Sequential treatment of TKIs and ICIs always accompanied with unexpected toxicity in NSCLC. • It is important to correctly sequence ICIs and TKIs for safe and effective clinical treatment. • Careful consideration should be given to the possibility of an increased risk of some adverse events when TKIs are pre/post-treated with ICIs. As more therapeutic targets are being discovered in advanced non-small cell lung cancer (NSCLC), it is pivotal for clinicians to correctly sequence immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) for delivery of safe and effective treatment. Our present study aimed to assess the safety profile of sequential treatment of TKIs and ICIs in advanced NSCLC. We retrospectively analyzed the data of 64 patients who underwent sequential treatment of EGFR/ALK-TKIs and ICIs, including all the EGFR/ALK-TKIs and ICIs approved by National Medical Products Administration (NMPA) in China. The decrease in hemoglobin was the most common adverse event (54.5 % and 44.4 %) for all patients. For TKIs post-treatment with ICIs group, the incidence rate of decrease in white blood cells was 32.7 %. Liver toxicity was also common for this sequential therapy: treatment-related elevation in ALT (30.9 %) and AST (25.5 %). In addition, grade 3 or higher skin toxicity occurred in 2 patients, and grade 3 or higher neuritis was observed in 1 patient. Interstitial pneumonia was also observed in 1 patient. For patients within the group of TKIs pre-treatment with ICIs, the most common adverse event was hepatic toxicity, the elevation in ALT and AST was 33.3 % and 22.2 % respectively. It was worth noting that the incidence rate of grade 3 or higher elevation in ALT and AST was 22.2 %. Other adverse events such as blood toxicity, skin rash, and diarrhea were also observed in this sequential treatment, but most of which was slight. Although the adverse event did not significantly increase in the sequential treatment pattern of our study, careful consideration should be given to the possibility of an increased risk of some adverse event when TKIs were pre/post-treated with ICIs. [ABSTRACT FROM AUTHOR]

Large cell neuroendocrine carcinoma of the lung (LCNEC) is a rare and highly aggressive type of lung cancer, with a complex biology that shares similarities with both small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC). The prognosis of LCNEC is poor, with a median overall survival of 8–12 months. The diagnosis of LCNEC requires the identification of neuroendocrine morphology and the expression of at least one of the neuroendocrine markers (chromogranin A, synaptophysin or CD56). In the last few years, the introduction of next-generation sequencing allowed the identification of molecular subtypes of LCNEC, with prognostic and potential therapeutic implications: one subtype is similar to SCLC (SCLC-like), while the other is similar to NSCLC (NSCLC-like). Because of LCNEC rarity, most evidence comes from small retrospective studies and treatment strategies that are extrapolated from those adopted in patients with SCLC and NSCLC. Nevertheless, limited but promising data about targeted therapies and immune checkpoint inhibitors in patients with LCNEC are emerging. LCNEC clinical management is still controversial and standardized treatment strategies are currently lacking. The aim of this manuscript is to review clinical and molecular data about LCNEC to better understand the optimal management and the potential prognostic and therapeutic implications of molecular subtypes. [ABSTRACT FROM AUTHOR]

Mutations in the mismatch repair (MMR) system predict the response to immune checkpoint inhibitors (ICIs) like colon or gastric cancer. However, the MMR system's involvement in non-small cell lung cancer (NSCLC) remains unknown. Addressing this issue will improve clinical guidelines in the case of mutations in the main genes of the MMR system (MLH1, MSH2, MSH6, and PMS2). This work retrospectively assessed the role that these gene mutations play in the response to and survival of ICIs in NSCLC. Patients with NSCLC treated with nivolumab as the second-line treatment in the University Hospital of Salamanca were enrolled in this study. Survival and response analyses were performed according to groups of MMR system gene expression (MMR expression present or deficiency) and other subgroups, such as toxicity. There was a statistically significant relationship between the best response obtained and the expression of the MMR system (p = 0.045). The presence of toxicity grade ≥ 3 was associated with the deficiency expression of MMR (dMMR/MSI-H) group (p = 0.022; odds ratio = 10.167, 95% confidence interval (CI) 1.669–61.919). A trend towards greater survival and response to ICIs was observed in NSCLC and dMMR. Assessing the genes in the MMR system involved in NSCLC is key to obtaining personalized immunotherapy treatments. [ABSTRACT FROM AUTHOR]