Endometrial cancer (EC) is rising both in incidence and mortality, is involving younger women, and is leading in the US for gynecologic cancer incidence. The application of molecular characterization and targeting treatment to selected molecular types of EC is exemplified by the marked benefit of mismatch repair deficient (dMMR) EC to immune checkpoint inhibitor (ICI) treatment. However, the response to immunotherapy has been less significant in other EC molecular types. We reported previously on the public health relevance of molecular analysis of endometrial cancer types to direct treatment considerations and discussed the limitation in biomarkers predictive of response to immunotherapy or available to examine for treatment selection, outside of mismatch repair deficiency. The current follow-on commentary addresses how new thinking can lead to optimization of immunotherapy applications for endometrial cancer molecular types, how to consider timing and sequencing of immunotherapy with other interventions, and directions for novel immunotherapy combinations. This report outlines key background studies and preclinical observations, directions to overcome inherent resistance, how to leverage ICI to augment clinical response to standard treatments, and considerations for how and when to re-expose patients to ICI treatment(s). The discussions led to potential clinical trial concepts now under development.

This study evaluates within-subject temporal differences between tumor and body temperatures using three cancer models: melanoma, breast cancer, and colon cancer, to monitor the effects of immunotherapy and chemotherapy on temperature differences. In the melanoma arm, TRP-2 immunotherapy led to increased tumor temperatures compared to the control group, with significant overall treatment separation observed at 58 h into the treatment protocol. For breast cancer, AC-Taxol chemotherapy resulted in a drop in body temperature for both treatment and control groups, with significant treatment group separation on tumor vs. body observed at 96 h. In colon cancer, anti-PD-1 immunotherapy showed an upward trend in tumor temperatures, with significant separation from the control group at 94 h. A series of statistical tests, including mixed-model repeated measures and non-parametric tests, revealed significant differences in temperature trends between treatment and control groups for all cancer types. Furthermore, examination of radial smoothing repeated measures models revealed how the clinical application of this technology could be applied. These results suggest that temperature-based monitoring may be an effective tool for assessing therapeutic responses in cancer treatments, highlighting the utility of thermal measurements in evaluating immunotherapy and chemotherapy efficacy.

To investigate the incidence of immune-related adverse events (irAEs) and corresponding perioperative outcomes among patients with colorectal cancer who received neoadjuvant immunotherapy and underwent curative radical resection. This was a retrospective, multicenter, real-world cohort study. A total of 452 patients with pathologically confirmed colorectal adenocarcinoma who completed neoadjuvant immunotherapy and curative radical surgery were enrolled from five tertiary hospitals between January 1, 2020 and December 31, 2024. The participating institutions included Beijing Friendship Hospital, Capital Medical University; Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; The Sixth Affiliated Hospital, Sun Yat-sen University; The First Affiliated Hospital of Nanchang University; and The Second Affiliated Hospital, Zhejiang University. The median age of the overall cohort was 58.5 years. In terms of clinical TNM staging, 86 patients (19.0%) were at stage Ⅱ and 366 (81.0%) were at stage Ⅲ. Based on MMR/MSI status, 116 patients (25.7%) were identified as deficient mismatch repair/high microsatellite instability (dMMR/MSI-H), and the remaining 336 (74.3%) as proficient mismatch repair/microsatellite stable (pMMR/MSS). Regarding treatment modalities, 92 patients (20.4%) received single-agent immune checkpoint inhibitor (ICI) therapy, 22 (4.9%) dual ICI combination therapy, 30 (6.6%) immunotherapy combined with chemotherapy, and 308 (68.1%) immunotherapy combined with chemoradiotherapy. All irAEs were graded in accordance with the Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0), and grade ≥3 irAEs were defined as severe irAEs. The primary outcomes were the overall incidence and organ-specific distribution of irAEs. Secondary outcomes covered irAE risks stratified by treatment regimens and MMR/MSI status, overall pathological complete response (pCR) rate, as well as perioperative clinical outcomes. Temporal trend analysis was conducted after logical validation of the initial onset time of irAEs. The overall incidence of all-grade irAEs reached 24.6% (111/452), including 73 cases (16.2%) of grade 1, 24 (5.3%) of grade 2, 7 (1.5%) of grade 3, 5(1.1%) of grade 4 and 2 (0.4%) of grade 5. Severe irAEs (grade ≥3) occurred in 14 patients, accounting for 3.1% of the total cohort. A total of 157 irAE episodes were documented, among which single-organ involvement was observed in 65 patients (58.6%) and multi-organ involvement in 46 patients (41.4%). The most frequently affected organ systems were skin and mucous membranes (40 episodes, 25.5%), endocrine and thyroid system (36 episodes, 22.9%), hematopoietic system (34 episodes, 21.7%), hepatobiliary system (21 episodes, 13.4%), and gastrointestinal tract (9 episodes, 5.7%). Other involved systems comprised musculoskeletal system (6 episodes, 3.8%), urinary and renal system (6 episodes, 3.8%), cardiovascular system (4 episodes, 2.5%), and general systemic reactions (1 episode, 0.6%). One fatal grade 5 event consisting of fulminant myocarditis complicated with malignant arrhythmia and liver failure was recorded. Stratified by treatment strategy, the incidence of all-grade irAEs was 23.9% (22/92) for single-agent ICI, 27.3% (6/22) for dual ICI combination, 23.3% (7/30) for immunochemotherapy and 24.7% (76/308) for immunochemoradiotherapy; the corresponding incidence of severe irAEs was 3.3%, 4.5%, 3.3%, and 2.9%, respectively. Univariate and multivariate regression analyses confirmed that MMR/MSI status was the only independent risk factor for irAE occurrence (OR=2.626,95%CI:1.566-4.402,<0.001). Validated complete onset time data were available for 85 patients, who were included in the temporal analysis, with 110 irAE episodes including 14 severe events identified. Approximately 58.8% (50/85) of irAEs emerged within 84 days after the first ICI administration, and 52.9% (45/85) developed one month after treatment cessation, including two grade 5 fatal events: severe myelosuppression/overlap syndrome following immunochemoradiotherapy, and fulminant myocarditis accompanied by malignant arrhythmia and liver failure after immunochemotherapy. The median time to first irAE onset was 61 (35-100) days. Among 14 severe irAEs, 9 events occurred after immunochemoradiotherapy, 3 after single-agent ICI therapy, 1 after dual ICI combination, and 1 after immuneochemotherapy. Apart from the 2 fatal cases, the other 11 severe irAEs were effectively alleviated via drug discontinuation, glucocorticoid intervention and/or supportive treatment, whereas one case of immune-related enteritis progressed into a chronic condition. No surgical delay of 14 days or longer attributed to irAEs was noted in the entire cohort. The median length of hospital stay was 14 (12-18) days in patients with irAEs versus 13 (11-16) days in those without irAEs, with no significant intergroup difference (=1.80, =0.072). The postoperative complication rates were 18.9% (21/111) and 18.5% (63/341) in the irAEs and non-irAEs groups, respectively, showing no statistical discrepancy (=0.01, >0.999). The overall pCR rate of all enrolled patients was 49.8% (225/452). IrAEs, which are mostly mild-to-moderate and manifest as multi-organ involvement, are not rare during neoadjuvant immunotherapy for colorectal cancer. Skin, endocrine and hematopoietic systems are the predominantly affected sites, and the majority of irAEs are clinically manageable. Although severe irAEs remain uncommon, they are featured with delayed onset and life-threatening potential; in particular, cardiovascular toxicities such as fulminant myocarditis warrant close clinical vigilance. The onset of irAEs is not confined to the conventional neoadjuvant treatment period, hence sustained safety monitoring is required throughout the perioperative phase and even after treatment completion.

To explore whether adjuvant immunotherapy can improve postoperative prognosis for non-small cell lung cancer (NSCLC) patients harboring oncogenic driver alterations beyond EGFR and ALK, a population with unclear benefit. Main inclusion criteria included resected NSCLC, stage IB-IIIB, and oncogenic driver alterations of KRAS mutation, ROS1 fusion, RET fusion, HER2 mutation, NTRK fusion, BRAF V600E mutation, and MET exon 14 skipping mutation. The positive PD-L1 cut-off was 1%. Adjuvant immunotherapy would be administered for one year or up to 16 cycles. Disease-free survival (DFS) after surgery was the endpoint. 190 patients with specific gene alterations were included, 25.8% of patients received adjuvant immunotherapy. The benefit from adjuvant immunotherapy in DFS was not observed in the overall population (hazard ratio [HR] 0.85, 95% confidence interval [CI 0.51-1.44, p = 0.551), while a numerical DFS benefit trend in the PD-L1-positive population was observed (HR 0.56, 95% CI 0.31-1.03, p = 0.059). After inverse probability of treatment weighting (IPTW) for the population with PD-L1 positivity who also received adjuvant chemotherapy, no statistical DFS benefit difference from adjuvant immunotherapy was observed between the KRAS (HR 0.29, 95% CI 0.10-0.88, p = 0.028) and non-KRAS mutation (HR 0.77, 95% CI 0.32-1.82, p = 0.549) subgroups (interaction p = 0.179), though with a marked numerical difference. Among the PD-L1-positive population, NSCLC harboring KRAS, MET exon 14 skipping, and BRAF V600E mutations showed a trend toward benefit from adjuvant immunotherapy, whereas NSCLC with HER2 mutation, RET fusion, and ROS1 fusion exhibited a weaker trend toward benefit. Patients with NSCLC harboring driver oncogenes other than EGFR/ALK and positive PD-L1 showed a trend toward benefiting from adjuvant immunotherapy. Although no significant interaction was observed, KRAS-mutant NSCLC demonstrated numerically superior DFS benefit compared with non-KRAS-mutant NSCLC.

Cancer immunotherapy has substantially advanced cancer treatment, achieving durable responses in select malignancies. However, its widespread application is limited by significant challenges: low efficacy in many solid tumors, severe side effects, and immune evasion facilitated by the tumor microenvironment (TME). Nanotechnology offers a promising approach to address these obstacles. By employing nanoparticles (NPs), we can precisely deliver therapeutics to tumor sites, ensure controlled release to minimize side effects, and amplify the immune response, thereby substantially boosting the effectiveness of immunotherapy. This review comprehensively highlights the latest advancements in using nanotechnology to enhance cancer immunotherapy. This paper details various applications of nanotech in this field. It discusses smart nanoparticles that respond to TME signals to release drugs (e.g., checkpoint inhibitors) directly at the tumor, reducing systemic side effects and activating T-cells. We also explore how nanovaccines, which co-deliver tumor markers and immune boosters, can induce antigen-specific immune responses. Furthermore, mRNA-loaded nanoparticles can directly modify CAR T-cells inside the body, simplifying treatment and increasing efficacy. Strategies like using PLGA NPs to deliver immune enhancers such as IL-2 are also presented, which activate immune cells while minimizing systemic issues. The review also explains how nanoparticles can re-engineer the immunosuppressive TME to create an environment more conducive to immune action. We also emphasize that nanotechnology-enhanced adoptive therapies, particularly cytokine-induced killer (CIK) cell immunotherapy, hold great potential to improve tumor targeting, treatment persistence durability, and overall anticancer efficacy. Collectively, we highlight synergistic effects achieved by combining nanoparticles with other treatments like chemotherapy, radiation, photothermal/photodynamic therapy, and more, which can turn hard-to-treat tumors into susceptible targets. The integration of nanotechnology and immunotherapy holds the potential to meaningfully advance future cancer therapy.

Immunotherapy has revolutionized cancer treatment, yet many patients show non-sensitivity. Here, we collected treatment-naïve samples from 190 esophageal squamous cell carcinoma (ESCC) patients undergoing anti-programmed death 1 (PD1) immunotherapy for proteome, phosphoproteome, and immunohistochemistry (IHC) analysis. Proteome-based stratification of ESCC identifies three proteomic subtypes (G-I-G-III) related to immunotherapy response and different molecular features, revealing that patients with high mitochondrial complex I protein expression show sensitivity to anti-PD1 immunotherapy. High mitochondrial complex I protein expression of ESCC cells or patient-derived organoids increases sensitivity to CD8 + T cell-mediated killing in the co-culture systems. Phosphoproteomic data analysis reveals YAP1 activation impairs immunotherapy efficacy. Inhibiting YAP1 or increasing mitochondrial complex I levels bolsters immunotherapy effectiveness in ESCC allograft tumors. Finally, we develop a highly accurate predictive model (AUC ≥ 0.90) by the signatures of mitochondrial complex I-mediated anti-tumor immune response and validate it in independent cohorts. This study provides a rich resource for investigating the mechanisms and indicators of immunotherapy in ESCC.

Immunotherapy has become a pivotal therapy for various cancers, including esophageal cancer, showing promising potential in improving survival rates and enabling personalized care. However, significant challenges occur in identifying predictive biomarkers, refining combination therapies, and managing immunotherapy-related adverse effects. This bibliometric study analyzed publications related to the use of immunotherapy in esophageal cancer management over a 10-y period (January 1, 2015, to October 14, 2024), retrieved from the Web of Science Core Collection. Keyword co-occurrence and co-citation analyses were performed to identify key contributors, central themes, and influential publications. A total of 545 publications on esophageal cancer immunotherapy were included in the analysis. A sharp increase in publication volume was observed beginning in 2019, with a peak between 2021 and 2023. China emerged as the leading contributor, accounting for 67.7% of the total output, while Zhengzhou University produced the highest number of publications among all institutions. Prominent individual contributors included Ken Kato and Shen Lin. Research hotspots centered on PD-1/PD-L1 inhibitors, combination therapies, and tumor microenvironment modulation. Notably, a clear temporal evolution in research focus was observed, with early studies emphasizing specific immune checkpoint targets and agents (e.g., PD-1, Pembrolizumab, and CTLA-4), followed by a shift toward mechanistic investigations involving the tumor microenvironment, treatment resistance, and prognosis. This study provides a comprehensive view of immunotherapy in the management of esophageal cancer, offering direction for future research and valuable insights for clinical innovation.

Cancer treatment has been revolutionized by immunotherapy and nanomedicine, offering innovative strategies to overcome the tumor microenvironment (TME) complexities. However, challenges such as therapeutic resistance, off-target effects, and immune suppression necessitate advanced delivery systems and combination approaches. Recent advancements in nanoparticle-based therapies, biomimetic platforms, and personalized immunotherapy provide promising solutions to enhance therapeutic efficacy while minimizing systemic toxicity. This review explores recent nanoparticle-mediated immunotherapy developments, highlighting strategies to optimize drug delivery, remodel the TME, and improve patient-specific treatment outcomes. A comprehensive review of recent literature focused on nanoparticle-based drug delivery, stimuli-responsive systems, biomimetic nanoplatforms, and personalized immunotherapy approaches. The effectiveness of combination therapies integrating physical and immunological strategies was also analyzed. Nanoparticle-mediated immunotherapy enables precise targeting and controlled drug release, significantly improving therapeutic outcomes. Biomimetic nanoplatforms enhance immune modulation and drug bioavailability, while personalized immunotherapy, guided by predictive biomarkers, tailors treatment to individual patients. Advanced nanomedicine strategies, including TME remodeling, targeted genome editing, and combination immunotherapies, offer promising avenues for overcoming limitations in conventional cancer treatments. Future research should optimize nanoformulations, integrate multi-modal treatment strategies, and refine biomarker-driven personalization to enhance clinical outcomes.

Simple Summary The management of locally advanced esophageal cancer poses considerable challenges and current strategies have significant risks. Moreover, despite various treatment regimens, response rates are inconsistent. In recent years, a new class of targeted therapy classified as ‘immunotherapy’ has changed the landscape of cancer management. The immune system is naturally designed to destroy malignant and aberrant cells; however, cancer cells have developed mechanisms to escape recognition. Immunotherapy, stimulates and enhances the patient’s own immune system, improving its ability to detect and eliminate cancerous cells more effectively. A thorough comprehension of how immunotherapy yields clinical benefit is intricately tied to the tumor microenvironment and its complex interactions across various pathways. Clinical trials have been conducted to determine the efficacy of immunotherapy in the management of esophageal cancer. This manuscript is aimed at understanding the evolving role of immunotherapy and esophageal cancer in both neoadjuvant and adjuvant settings to assist in the clinical decision making process. Abstract Locally advanced esophageal cancer (LAEC) poses a significant and persistent challenge in terms of effective treatment. Traditionally, the primary strategy for managing LAEC has involved concurrent neoadjuvant chemoradiation followed by surgery. However, achieving a pathologic complete response (pCR) has proven to be inconsistent, and despite treatment, roughly half of patients experience locoregional recurrence or metastasis. Consequently, there has been a paradigm shift towards exploring the potential of immunotherapy in reshaping the landscape of LAEC management. Recent research has particularly focused on immune checkpoint inhibitors, investigating their application in both neoadjuvant and adjuvant settings. These inhibitors, designed to block specific proteins in immune cells, are meant to enhance the immune system’s ability to target and combat cancer cells. Emerging evidence from these studies suggests the possibility of a mortality benefit, indicating that immunotherapy may contribute to improved overall survival rates for individuals grappling with esophageal cancer. This manuscript aims to meticulously review the existing literature surrounding neoadjuvant and adjuvant immunotherapy in the context of LAEC management. The intention is to thoroughly examine the methodologies and findings of relevant studies, providing a comprehensive synthesis of the current understanding of the impact of immunotherapy on esophageal cancer.

INTRODUCTION PDT can interfere with cytokine-mediated responses that play an important role in the processes of cancer progression, tumor angiogenesis and metastasis. Therefore, based on the identification of these cancer biomarkers, the therapy of combining various forms of treatment, including immunotherapy and PDT, may be a justified strategy for colorectal cancer treatment that focuses on individualized comprehensive therapy. METHOD We reviewed the major approaches on the use of immunotherapy in colorectal cancer, with the special regard to photodynamic therapy, its immunological effect and new oncological treatment directions, connected with adjuvant immunotherapy including use of nanoparticles. Databases such as PubMed, ScienceDirect and Springer were utilized to search the literature for relevant articles. PURPOSE To review studies of the immunotherapy in colon cancer and immune response to PDT. CONCLUSION Based on the identification of immunological cancer biomarkers, the therapy of combining various forms of treatment, including immunotherapy and PDT, may be a justified strategy for colorectal cancer treatment that focuses on individualized comprehensive therapy.