Immunotherapy For Advanced Cancer Research Articles

Molecular correlates of response to immunotherapy in advanced or recurrent endometrial cancer: A pilot study

Molecular correlates of response to immunotherapy in advanced or recurrent endometrial cancer: A pilot study

Unraveling the potential biomarkers of immune checkpoint inhibitors in advanced ovarian cancer: a comprehensive review.

The ongoing research on the role of immunotherapy in advanced ovarian cancer (OC) and current clinical trials indicate that patients shown limited response to immune checkpoint inhibitor (ICI) monotherapy. When combined with other treatments or drugs, the efficacy of immunotherapy will be significantly improved. Biomarkers can be used to identify patients with better responses, thereby improving the precision and efficacy of immunotherapy. Key biomarkers for advanced OC include homologous repair deficiency, programmed death-ligand (PD-L) 1 expression, chemokines, and tumor infiltrating lymphocytes. These biomarkers could be applied in the future to select the most suitable patient populations. This review comprehensively examines the research and development of biomarkers in OC immunotherapy from three omics perspectives: genomics, transcriptomics, and proteomics, which may provide guidance for the effectiveness of OC immunotherapy strategies.

Advancing Cancer Immunotherapy through Engineering New PD-L1 Degraders: A Comprehensive Study from Small Molecules to PD-L1-Specific Peptide-Drug Conjugates.

Despite the considerable achievements of antibodies targeting PD-1/PD-L1 in cancer immunotherapy, limitations in antitumor immune response and pharmacokinetics hinder their clinical adoption. Small molecules toward PD-L1 degradation signifies an innovative avenue to modulate PD-1/PD-L1 axis. Herein, we unveil a comprehensive engineering involving the development of new PD-L1 degraders based on the berberine (BBR) and palmatine (PMT) bioactive frameworks and explore their translational potential for cancer immunotherapy using a peptide-drug conjugate strategy. Chemical modifications at the O-9 position of PMT dramatically enhance the PD-L1 degradation capacity. Further conjugation of PMT degraders with an anti-PD-L1 peptide featuring disulfide linkers enables efficient GSH-specific prodrug activation, yielding synergistic immunotherapeutic benefits through both external PD-L1 blockade and internal PD-L1 degradation mechanisms. This work elucidates the compelling charm of the discovery and application of PD-L1 degraders, offering solutions to the challenges in advancing cancer immunotherapy in widespread clinics.

Longitudinal liquid biopsy predicts clinical benefit from immunotherapy in advanced non-small cell lung cancer

High heterogeneity in clinical benefit characterizes the use of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC). We prospectively enrolled 113 advanced NSCLC patients treated with ICIs and performed liquid biopsy at the time of ICI start (T1), after 3 weeks (T2) and at the time of radiological evaluation (T3). Molecular variables were associated with outcome endpoints: cfDNA quantification, its dynamic change (∆T2–T1), variant allele frequency (VAF) of the gene with the highest frequency detected at baseline with NGS (maxVAF) and its dynamic change (∆T2–T1). At multivariate analysis, PD-L1 negativity, T1 cfDNA, cfDNA increase (∆T2–T1), and T2 VAF were significantly associated with shorter progression-free survival (PFS); PD-L1 negativity, squamous histology, T1 cfDNA, cfDNA (∆T2–T1) increase, and T2 maxVAF affected overall survival (OS). Among high PD-L1 expressing patients treated in first-line, elevated T2 maxVAF and cfDNA increase (∆T2–T1) correlated with worse PFS; higher T2 maxVAF and cfDNA increase (∆T2–T1) with worse OS. Derived integrated models were used to build nomograms and categorize different risk groups.

Heterogeneity in peripheral blood immune lymphocyte subsets predicts the response of immunotherapy or chemoradiotherapy in advanced lung cancer: an analysis across different pathological types, treatment modalities and age

Heterogeneity in peripheral blood immune lymphocyte subsets predicts the response of immunotherapy or chemoradiotherapy in advanced lung cancer: an analysis across different pathological types, treatment modalities and age

Revealing the mechanism of natural product-induced immunogenic cell death: opening a new chapter in tumor immunotherapy.

This review underscores the role of natural products in inducing immunogenic cell death (ICD) as a key strategy in tumor immunotherapy. It reveals that natural products can activate ICD through multiple pathways-apoptosis, autophagy, pyroptosis, and necroptosis-leading to the release of danger-associated molecular patterns (DAMPs), dendritic cell activation, and improved antigen presentation, which together stimulate a potent anti-tumor immune response. The study also demonstrates the enhanced therapeutic potential of combining natural products with immune checkpoint inhibitors. With a focus on translating preclinical findings into clinical practice, this review consolidates recent discoveries and suggests future research paths, offering both theoretical insights and practical guidance for advancing cancer immunotherapy.

Activation of NOD1 on tumor-associated macrophages augments CD8+ T cell-mediated antitumor immunity in hepatocellular carcinoma.

The efficacy of immunotherapy targeting the PD-1/PD-L1 pathway in hepatocellular carcinoma (HCC) is limited. NOD-like receptors (NLRs) comprise a highly evolutionarily conserved family of cytosolic bacterial sensors, yet their impact on antitumor immunity against HCC remains unclear. In this study, we uncovered that NOD1, a well-studied member of NLR family, exhibits predominant expression in tumor-associated macrophages (TAMs) and correlates positively with improved prognosis and responses to anti-PD-1 treatments in patients with HCC. Activation of NOD1 in vivo augments antitumor immunity and enhances the effectiveness of anti-PD-1 therapy. Mechanistically, NOD1 activation resulted in diminished expression of perilipin 5, thereby hindering fatty acid oxidation and inducing free fatty acid accumulation in TAMs. This metabolic alteration promoted membrane localization of the costimulatory molecule OX40L in a lipid modification-dependent manner, thereby activating CD8+ T cells. These findings unveil a previously unrecognized role for NOD1 in fortifying antitumor T cell immunity in HCC, potentially advancing cancer immunotherapy.

B-343 Development of CD40 and HER2 Bispecific Antibodies for Enhanced Efficacy against HER2-Positive Tumors

Abstract Background CD40, a member of the tumor necrosis factor superfamily, is primarily expressed on antigen-presenting cells. This receptor plays a crucial role in facilitating the interaction between dendritic cells, activating antigen-specific T cells. Agonist antibodies targeting the CD40 receptor have the potential to mimic the natural CD40 ligand, fostering dendritic cell maturation and stimulating immunity against “cold” tumors. Although this approach has shown promise in preclinical studies, translating it to clinical success has been challenging. Only modest anti-tumor activity was observed in cancer patients, and none of the developed CD40 monoclonal antibodies (mAbs) progressed beyond early clinical trials, highlighting a need for improved anti-tumor efficacy. Methods In this study, we successfully developed an anti-human CD40 agonist rabbit monoclonal antibody using Yurogen's proprietary SMAB(TM) platform. The most potent CD40 mAb clone was combined with trastuzumab (an anti-HER2 mAb) to create a therapeutic bispecific antibody. Our goal is to leverage immune cell activation through HER2-targeted cancer therapy to achieve enhanced anti-tumor activity. Dozens of diverse CD40xHER2 bispecific antibody designs (both symmetry and asymmetry) were explored, with careful evaluation of expression yield, purity, and binding profiles for each target respectively. Results A few bispecific antibody designs demonstrated robust binding to both HER2 and CD40 antigen proteins, as well as receptor-expressing cell lines. Notably, two developed bispecific antibodies exhibited potent killing of HER2-positive cancer cells with the assistance of innate immune cells. Conclusions In sum, this study provides novel insights into designing bispecific antibodies against HER2 and CD40, offering a promising avenue for advancing cancer immunotherapy.

Developing an erythrocyte‒MHC-I conjugate for cancer treatment.

Mature erythrocytes are known to lack major histocompatibility complex (MHC) proteins. However, the presence of MHC molecules on erythrocytes has been occasionally reported, though without a defined function. In this study, we designed erythrocyte conjugated solely with a fusion protein consisting of an antigenic peptide linked to MHC class I (MHC-I) protein, termed MHC-I‒Ery. The modified erythrocyte, decorated with the peptide derived from human papillomavirus (HPV) 16 oncoprotein E6/E7, effectively activated antigen-specific CD8+ T cells in peripheral blood mononuclear cells (PBMCs) from HPV16+ cervical cancer patients. Additionally, MHC-I‒Ery monotherapy was shown to inhibit antigen-positive tumor growth in mice. This treatment immediately activated CD8+ T cells and reduced suppressive myeloid cells in the spleen, leading to systemic anti-tumor activity. Safety and tolerability evaluations of MHC-I‒Ery in non-human primates further supported its clinical potential. Our results first demonstrated that erythrocytes equipped solely with antigen peptide‒MHC-I complexes can robustly stimulate the immune system, suggesting a novel and promising approach for advancing cancer immunotherapy.

Incidence of hematological toxicity with use of immunotherapy and chemotherapy in advanced non-small cell lung cancer.

Incidence of hematological toxicity with use of immunotherapy and chemotherapy in advanced non-small cell lung cancer.

Treatment options for tumor progression after initial immunotherapy in advanced non-small cell lung cancer: A real-world study

ObjectiveWhether to continue administering immunotherapy to patients with advanced non-small cell lung cancer (NSCLC) who have experienced tumor progression remains controversial after immunotherapy. The aims were to explore survival outcomes after further immunotherapy post-progression and to determine the optimal combination therapy in such cases. MethodsOverall, 507 patients with NSCLC who underwent immunotherapy and experienced tumor progression were retrospectively divided into Immuno-combination and No-immuno groups according to whether additional combination therapy involving immunotherapy was administered post-progression. Progression-free survival (PFS) and overall survival (OS) were evaluated. Subgroup analyses were performed according to the different treatment regimens for patients in the Immuno-combination group. ResultsAfter propensity score matching, there were 150 patients in the No-immuno group and 300 patients in the Immuno combination group. Superior PFS was observed in the Immuno-combination group compared with those in the No-immuno group (6-month PFS: 25.3 % vs. 60.6 %; 12-month PFS: 6.7 % vs. 24.4 %; P < 0.001). Similar intergroup differences were observed for OS (12-month OS: 22.3 % vs. 69.4 %; 18-month OS: 6.4 % vs. 40.4 %; P < 0.001). Superior PFS outcomes were observed in the Immuno+Antiangiogenic group compared with the Immuno+Chemo group (6-month PFS: 51.3 % vs. 71.5 %; 12-month PFS: 23.1 % vs. 25.7 %; P = 0.017). Similar differences in OS were observed between those same subgroups (12-month OS: 62.1 % vs. 77.9 %; 18-month OS: 33.3 % vs. 48.7 %; P = 0.006). ConclusionPatients with NSCLC experiencing tumor progression post-immunotherapy can still benefit from further treatment, with immunotherapy combined with antiangiogenic therapy the most efficacious option.

402P Inflammatory biomarkers for predicting the efficacy of immunotherapy in advanced breast cancer

402P Inflammatory biomarkers for predicting the efficacy of immunotherapy in advanced breast cancer

Symptom clusters and network analysis of patients with intermediate and advanced liver cancer treated with targeted immunotherapy.

This study aims to identify symptom clusters in patients with intermediate and advanced liver cancer receiving targeted immunotherapy, focusing on core and bridge symptoms to establish a foundation for precise symptom management. This study used a cross-sectional survey and utilized convenience sampling from May 2023 to January 2024 at a third-class hospital in Shanghai, China. The severity of symptoms in liver cancer patients during treatment was evaluated using the Memorial Symptom Assessment Scale. Network analysis was employed to depict the interrelation of symptom clusters and identify core and bridge symptoms. The symptoms were classified by severity into five clusters: oral, gastrointestinal, fatigue-related, body image, and pain-sleep. Within the symptom network, the core symptoms were pain, "I don't look like myself," and nausea, while the critical bridge symptoms included pain, itching, and feeling bloated. The strongest connections were observed between nausea and vomiting, followed by taste changes and dry mouth, as well as weight loss and "I don't look like myself." In patients receiving targeted immunotherapy for intermediate and advanced liver cancer, multiple symptoms can emerge simultaneously, forming interconnected clusters. By identifying and intervening in core and bridge symptoms, personalized management strategies can be developed to relieve other symptoms and disrupt connections between symptom clusters, thereby enhancing symptom management efficacy. This study has significant clinical and research implications, offering new insights to improve patients' quality of life and treatment outcomes.

Investigating the Immune-Stimulating Potential of β-Glucan from Aureobasidium pullulans in Cancer Immunotherapy.

β-glucan, a polysaccharide found in various sources, exhibits unique physicochemical properties, yet its high polymerization limits clinical applications because of its solubility. Addressing this limitation, we introduce PPTEE-glycan, a highly purified soluble β-1,3/1,6-glucan derived from Aureobasidium pullulans. The refined PPTEE-glycan demonstrated robust immune stimulation in vitro, activated dendritic cells, and enhanced co-stimulatory markers, cytokines, and cross-presentation. Formulated as a PPTEE + microemulsion (ME), it elevated immune responses in vivo, promoting antigen-specific antibodies and CD8+ T cell proliferation. Intratumoral administration of PPTEE + ME in tumor-bearing mice induced notable tumor regression, which was linked to the activation of immunosuppressive cells. This study highlights the potential of high-purity Aureobasidium pullulans-derived β-glucan, particularly PPTEE, as promising immune adjuvants, offering novel avenues for advancing cancer immunotherapy.

Radiotherapy for patients with locally advanced esophageal squamous cell carcinoma receiving neoadjuvant immunotherapy combined with chemotherapy

With the success of immunotherapy in advanced esophageal cancer, neoadjuvant chemo-immunotherapy (CIT) is being increasingly used for local staged esophageal cancer, especially in the context of clinical trials, which brings similar pCR with neoadjuvant chemoradiotherapy and shows promising results. However, there is still a part of potentially operable patients can't undergo surgery after neoadjuvant chemo-immunotherapy. The follow-up treatment and prognosis of this population remain unclear. Patients pathologically diagnosed with ESCC, clinical stage T1-3N+M0 or T3-4aNanyM0 (AJCC 8th), PS 0–1 were retrospectively enrolled from 1/2020 to 6/2021 in Zhejiang Cancer Hospital. All patients firstly received PD-1 inhibitors plus chemotherapy (albumin paclitaxel, 260 mg/m2 on day 1 plus carboplatin AUC = 5 on day 1) every 3 weeks for 2–4 cycles. For those patients who did not receive surgery, definitive radiotherapy with 50.4 Gy/28F or 50 Gy/25F was adopted using VMAT, concurrent with chemotherapy or alone. The concurrent chemotherapy regimens included weekly TC (paclitaxel 50 mg/m2, d1, carboplatin AUC = 2, d1) or S1 (60 mg bid d1–14, 29–42). The survival outcomes and treatment toxicity were recorded and analyzed. A total of 56 eligible patients were finally identified from 558 patients who were treated in department of thoracic surgery, among all the patients, 25 (44.6%) received radiotherapy alone, and 31 (55.4%) received chemoradiotherapy after neoadjuvant CIT. The median follow-up was 20.4 months (interquartile range [IQR] 8.7–27 months). The median PFS and OS were 17.9 months (95% confidence interval [CI] 11.0–21.9 months) and 20.5 months (95% CI 11.8–27.9 months), respectively. In the subgroup analysis, the median OS was 26.3 months (95% CI 15.33–NA) for patients exhibiting partial response (PR) to CIT, compared to 17 months (95% CI 8.77–26.4) for those with stable disease (SD) or progressive disease (PD), yielding a hazard ratio (HR) of 0.54 (95% CI 0.27–1.06, P = 0.07). No significant difference was observed for patients received radiotherapy alone or chemoradiotherapy with HR = 0.73 (95% CI 0.72–2.6, P = 0.33). The most common Adverse events (AEs) observed during this study were anemia (98.2%), leukopenia (83.9%), thrombocytopenia (53.6%). AEs of grade ≥ 3 radiation-induced pneumonitis and esophagitis were 12.5% and 32.1%, especially, 6 patients (10.7%) died from esophageal fistula and 2 patients (3.6%) died from grade 5 pneumonitis. For local advanced ESCC patients after neoadjuvant CIT who did not receive surgery, definitive radiotherapy was an optional treatment strategy. However, those patients with no response to CIT also showed poor response to radiotherapy, and particular attention should be paid to treatment related toxicity, especially esophageal fistula.

Engineering Versatile Bacteria-Derived Outer Membrane Vesicles: An Adaptable Platform for Advancing Cancer Immunotherapy.

In recent years, cancer immunotherapy has undergone a transformative shift toward personalized and targeted therapeutic strategies. Bacteria-derived outer membrane vesicles (OMVs) have emerged as a promising and adaptable platform for cancer immunotherapy due to their unique properties, including natural immunogenicity and the ability to be engineered for specific therapeutic purposes. In this review, a comprehensive overview is provided of state-of-the-art techniques and methodologies employed in the engineering of versatile OMVs for cancer immunotherapy. Beginning by exploring the biogenesis and composition of OMVs, unveiling their intrinsic immunogenic properties for therapeutic appeal. Subsequently, innovative approaches employed to engineer OMVs are delved into, ranging from the genetic engineering of parent bacteria to the incorporation of functional molecules. The importance of rational design strategies is highlighted to enhance the immunogenicity and specificity of OMVs, allowing tailoring for diverse cancer types. Furthermore, insights into clinical studies and potential challenges utilizing OMVs as cancer vaccines or adjuvants are also provided, offering a comprehensive assessment of the current landscape and future prospects. Overall, this review provides valuable insights for researchers involved in the rapidly evolving field of cancer immunotherapy, offering a roadmap for harnessing the full potential of OMVs as a versatile and adaptable platform for cancer treatment.

The Association between Lymphocytic Thyroiditis and Papillary Thyroid Cancer Harboring Mutant BRAF: A Systematic Review and Meta-Analysis.

Background: Papillary thyroid cancer (PTC) and lymphocytic thyroiditis (LT) co-occur with a prevalence of about 30%. PTC harboring BRAFV600E (PTC-BRAF) confers a worse prognosis, but it is unclear if LT alters prognostic features and recurrence of PTC. Objective: We compared the prevalence of PTC-BRAF with and without LT. The risk of adverse pathological features in (i) PTC in the presence and absence of BRAF mutation, irrespective of LT status, was compared to (ii) PTC in the presence and absence of LT, irrespective of BRAF status. Methods: We searched PubMed, Embase, and Web of Science Core Collection for observational studies published from 2010 to June 2023 on adult patients with PTC. The search strategy yielded 47 studies with relevant data. Data of baseline characteristics, clinicopathological features, and the quality assessment tool were extracted by two reviewers. The study was registered with PROSPERO (CRD42023437492). Results: Of the 47 studies, 39 studies with a total cohort of 28 143, demonstrated that the odds of PTC-BRAF were significantly lower in the presence of LT compared to its absence (odds ratio [OR] 0.53, 95% confidence interval [CI]: 0.48-0.58, p < 0.00001). In PTC-BRAF patients, there was a positive association of central neck nodal disease (CNND), PTC > 1 cm, extra-thyroidal extension, American Joint Committee on Cancer (AJCC) Stage 3-4, and multifocality with pooled ORs of 1.54 (95% CI: 1.16-2.04), 1.14 (95% CI: 0.82-1.58), 1.66 (95% CI: 1.40-1.97), 1.53 (95% CI: 1.35-1.75), and 1.24 (95% CI: 1.11-1.40) respectively, compared to wild-type PTC, irrespective of LT status. In the same studies, PTC with LT patients had lower pooled ORs of 0.64 (95% CI: 0.51-0.81) for CNND, 0.83 (95% CI: 0.73-0.95) for PTC > 1 cm, 0.71 (95% CI: 0.58-0.86) for ETE, 0.84 (95% CI: 0.75-0.94) for AJCC Stage 3-4 compared to PTC without LT, irrespective of BRAF status. PTC recurrence was not affected by BRAF or LT, with pooled ORs of 1.12 (95% CI: 0.66-1.90, p = 0.67) and 0.60 (95% CI: 0.28-1.30, p = 0.20) respectively. Similar results were seen with recurrence expressed as hazard ratio in this limited data-set. Conclusion: The odds of PTC-BRAF are significantly lower in the presence of LT than without. PTC with LT, irrespective of BRAF status, was significantly associated with better prognostic factors. Further studies are required to evaluate if LT inhibits PTC-BRAF, and whether this is relevant to the role of immunotherapy in advanced thyroid cancer.

KRAS and TP53 co-mutation predicts benefit of immune checkpoint blockade in lung adenocarcinoma

BackgroundPredictive biomarkers in use for immunotherapy in advanced non-small cell lung cancer are of limited sensitivity and specificity. We analysed the potential of activating KRAS and pathogenic TP53 mutations to provide additional predictive information.MethodsThe study cohort included 713 consecutive immunotherapy patients with advanced lung adenocarcinomas, negative for actionable genetic alterations. Additionally, two previously published immunotherapy and two surgical patient cohorts were analyzed. Therapy benefit was stratified by KRAS and TP53 mutations. Molecular characteristics underlying KRASmut/TP53mut tumours were revealed by the analysis of TCGA data.ResultsAn interaction between KRAS and TP53 mutations was observed in univariate and multivariate analyses of overall survival (Hazard ratio [HR] = 0.56, p = 0.0044 and HR = 0.53, p = 0.0021) resulting in a stronger benefit for KRASmut/TP53mut tumours (HR = 0.71, CI 0.55–0.92). This observation was confirmed in immunotherapy cohorts but not observed in surgical cohorts. Tumour mutational burden, proliferation, and PD-L1 mRNA were significantly higher in TP53-mutated tumours, regardless of KRAS status. Genome-wide expression analysis revealed 64 genes, including CX3CL1 (fractalkine), as specific transcriptomic characteristic of KRASmut/TP53mut tumours.ConclusionsKRAS/TP53 co-mutation predicts ICI benefit in univariate and multivariate survival analyses and is associated with unique molecular tumour features. Mutation testing of the two genes can be easily implemented using small NGS panels.

Nano-Delivery of Immunogenic Cell Death Inducers and Immune Checkpoint Blockade Agents: Single-Nanostructure Strategies for Enhancing Immunotherapy.

Cancer immunotherapy has revolutionized oncology by harnessing the patient's immune system to target and eliminate cancer cells. However, immune checkpoint blockades (ICBs) face limitations such as low response rates, particularly in immunologically 'cold' tumors. Enhancing tumor immunogenicity through immunogenic cell death (ICD) inducers and advanced drug delivery systems represents a promising solution. This review discusses the development and application of various nanocarriers, including polymeric nanoparticles, liposomes, peptide-based nanoparticles, and inorganic nanoparticles, designed to deliver ICD inducers and ICBs effectively. These nanocarriers improve therapeutic outcomes by converting cold tumors into hot tumors, thus enhancing immune responses and reducing systemic toxicity. By focusing on single-nanoparticle systems that co-deliver both ICD inducers and ICBs, this review highlights their potential in achieving higher drug concentrations at tumor sites, improving pharmacokinetics and pharmacodynamics, and facilitating clinical translation. Future research should aim to optimize these nanocarrier systems for better in vivo performance and clinical applications, ultimately advancing cancer immunotherapy.

Radiotherapy improved the efficacy of immunotherapy for advanced esophageal cancer.

e16063 Background: The development of immunotherapy has changed treatment methods for advanced esophageal cancer (EC).However, the efficacy of ICIs in advanced EC is not ideal, and the clinical research on the combination of ICIs and Radiotherapy(RT) in advanced EC remains insufficient. This study aimed to evaluate the effectiveness and safety of radiation in first-line immunotherapy for advanced EC. Methods: We conducted 201 advanced EC patients who received first-line ICIs in West China Hospital. The enrolled patients were divided into 2 groups based on whether they received radiation therapy. Results: The analysis included data from 201 patients. The radiotherapy (RT) group had 103 patients (51.2%), whereas the non-radiotherapy (NRT) group included 98 individuals (48.8%). The RT sites include esophagus lesions (83, 80.6%), metastatic lymph nodes (11, 10.7%), liver metastases (4, 3.9%), bone metastases (2, 1.9%), brain metastases (2, 1.9%), lung metastases(1, 0.97%). The median radiation dose was 50.4 Gy (range, 12-68). The RT group had a median OS of 22.8 months (95% CI, 17.8-NA), which was longer than the NRT group's 14.6 months (95% CI, 12.8-26.5) (p = 0.038). And the median PFS was 12.9 months (95% CI, 11.2-14.0) in the RT group versus 7.3 months (95% CI, 6.3-9.7) in the NRT group (p = 0.006). Patients in the RT group had a higher disease control rate (DCR) (99.0% vs. 76.5%, P &lt; 0.001). However, a higher proportion of patients in the RT group developed grade 3-4 myelosuppression (37.86% V.S. 20.20%, P = 0.006), and there was no significant difference in the other AEs. Conclusions: In the first-line immunotherapy for advanced esophageal cancer, radiotherapy has been attributed to improved survival with tolerable toxicity.