Clinicopathological and prognostic significance of VEGF, PDGF-B, and HER2/neu expression in gallbladder cancer.

AIM: Gallbladder cancer (GBC) is usually diagnosed in advanced stages with poor survival. The molecular mechanisms of GBC still remain unexplored. Several angiogenesis factors play a pivotal role in tumor progression. We aimed to study the expression of VEGF, PDGF-B, and human epidermal growth factor receptor 2 (HER2/neu) and its association with clinicopathological features and survival in GBC. MATERIALS AND METHODS: VEGF, PDGF-B, and HER2/neu expression was studied by immunohistochemistry (IHC) after histological evaluation in 91 GBC cases. The relationship between these markers and clinicopathological features and survival was explained through the Cox regression model and Kaplan-Meier method. RESULTS: VEGF, PDGF-B, and HER2/neu overexpressed in 45, 79, and 68% GBC cases, respectively. VEGF was significantly overexpressed in GBC without gall stones (GS) (p = 0.007) and with moderately and poorly differentiated tumors (p = 0.012). HER2/neu was significantly overexpressed in GBC with GS (p = 0.022). Median overall survival (OS) was 39 months (95% CI: 23-55). In univariate analysis, histological type (adenocarcinoma and papillary) vs. others (signet ring/mucinous/adenosquamous) (p = 0.004), depth of tumor infiltration (p = 0.017), distant metastasis (p = 0.012), and adjuvant therapies (chemotherapy/radiotherapy) (p = 0.083) were associated with poor prognosis. Multivariate survival analysis showed histological type (p = 0.004) and distant metastasis (p = 0.032) to be independent prognostic factors for OS. Histological type (p = 0.002), distant metastasis (p = 0.003), and depth of tumor infiltration (T3-T4) (p = 0.012) showed poor median survival. Poor survival was seen in VEGF and HER2/neu positive cases. CONCLUSION: Overexpression of VEGF, PDGF-B, and HER2/neu might be possible prognostic biomarkers in GBC. Poor survival of VEGF and HER2/neu positive cases indicates the possibilities of using their blockers as therapeutic agents.

Neuroendocrine neoplasms of the gallbladder: A single institute analysis of outcomes and prognostic factors.

INTRODUCTION: Neuroendocrine neoplasms (NENs) are classified as neuroendocrine tumors (NETs), neuroendocrine carcinomas (NECs), and mixed neuroendocrine and nonneuroendocrine neoplasms (MiNENs) according to World Health Organization classification. We present our experience of NENs of the gallbladder (GB) from a high-volume cancer hospital. MATERIALS AND METHODS: The present study is a retrospective analysis of all patients with GB NENs who presented between January 2015 and June 2023. The patient details and treatment received with follow-up were noted. The primary endpoint was overall survival (OS). RESULTS: A total of 147 patients were included in the study. The median age was 52 (27-81) years. There was a female predominance (70.7%). NEC was the most common subtype (84.4%) followed by MiNEN (12.9%) and NET (2.7%). The most common stage at presentation was metastatic (70.7%) followed by locally advanced (21.8%), and early disease (7.5%). The median follow-up was 9.92 (1.77-76.06) months. Median OS was 6.14 (3.93-8.35) months. Median OS in patients who received multimodality treatment was 20.20 (17.99-22.41) months versus 4.00 (2.91-5.10) months in those who did not receive it. CONCLUSION: GB NENs are rare, but aggressive tumors with NEC being the most common type. Multimodality treatment yields favorable outcomes. However, the development of better systemic therapy is needed to help improve survival further.

Single-cell characterization of infiltrating T cells identifies novel targets for gallbladder cancer immunotherapy.

Gallbladder cancer (GBC) is among the most common malignancies of biliary tract system due to its limited treatments. The immunotherapeutic targets for T cells are appealing, however, heterogeneity of T cells hinds its further development. We systematically construct T cell atlas by single-cell RNA sequencing; and utilized the identified gene signatures of high_CNV_T cells to predict molecular subtyping towards personalized therapeutic treatments for GBC. We identified 12 T cell subtypes, where exhausted CD8+ T cells, activated/exhausted CD8+ T cells, and regulatory T cells were predominant in tumors. There appeared to be an inverse relationship between Th17 and Treg populations with Th17 levels significantly reduced, whereas Tregs were concomitantly increased. Furthermore, we first established subtyping criterion to identify three subtypes of GBC based on their pro-tumorigenic microenvironments, e.g., the type 1 group shows more M2 macrophages infiltration, while the type 2 group is infiltrated by highly exhausted CD8+ T cells, B cells and Tregs with suppressive activities. Our study provides valuable insights into T cell heterogeneity and suggests that molecular subtyping based on T cells might provide a potential immunotherapeutic strategy to improve GBC treatment.

Construction and validation of the predictive model for gallbladder cancer liver metastasis patients: a SEER-based study.

BACKGROUND: The purpose of this present research was to construct a nomograph model to predict prognosis in gallbladder cancer liver metastasis (GCLM) patients so as to provide a basis for clinical decision-making. METHODS: We surveyed patients diagnosed with GCLM in the Surveillance Epidemiology and the End Results database between 2010 and 2019. They were randomized 7 : 3 into a training set and a validation set. In the training set, meaningful prognostic factors were determined using univariate and multivariate Cox regression analyses, and an individualized nomogram prediction model was generated. The prediction model was evaluated by C-index, calibration curve, ROC curve and DCA curve from the training set and the validation set. RESULTS: A total of 727 confirmed cases were enrolled in the research, 510 in the training set and 217 in the validation set. Factors including bone metastasis, surgery, chemotherapy and radiotherapy were independent prognostic factors for cancer-specific survival (CSS) rates and were employed in the construction of the nomogram model. The C-index for the training set and validation set were 0.688 and 0.708, respectively. The calibration curve exhibited good consistency between predicted and actual CSS rates. ROC curve and DCA of the nomogram showed superior performance at 6 months CSS, 1-year CSS and 2 years CSS in both the training set and validation set. CONCLUSION: We have successfully constructed a nomogram model that can predict CSS rates in patients with GCLM. This prediction model can help patients in counseling and guide clinicians in treatment decisions.

Long non­coding RNAs in gallbladder cancer: From mechanisms to therapeutic opportunities (Review).

Due to the lack of specific symptoms, characteristic diagnostic markers and effective comprehensive treatment, gallbladder cancer (GBC) is currently considered one of the most malignant abdominal tumors. With the rapid development of biological technologies, long non­coding RNAs (lncRNAs), once regarded as transcriptional junk, have been demonstrated to participate in almost the whole process of the central dogma of molecular biology. The central dogma deals with the transfer of sequential information at the level of individual residues. LncRNAs have an effect on multiple cancer types. However, evidence of dysregulated lncRNA functions in GBC is limited. In the present review, the regulatory mechanisms of lncRNA function on gene expression were examined, including epigenetic modification, transcriptional regulation and post­translational modulation. These mechanisms are strongly associated with tumor development and metastasis. Next, it was summarized how lncRNAs affect GBC diverse malignant phenotypes through various mechanisms. Moreover, predictions of lncRNA interactions with other functional molecules in malignancies were made using several valuable databases, including crosstalk between lncRNA and DNA, mRNA, microRNA, and protein. Additionally, several potential therapeutic methods targeting pathological lncRNAs in tumors were identified. Finally, perspectives about lncRNA research and applications in GBC were presented in the current study, including viewpoints of coding potential of lncRNAs and feasible usage of micropeptides encoded by lncRNAs; roles of lncRNAs in tumor cell metabolic reprogramming and tumor microenvironment; and function of lncRNAs as possible biomarkers and therapeutic targets for improving GBC diagnosis, treatment and prognosis.

Cáncer incidental de vesícula biliar tras Colecistectomía Laparoscópica / Incidental gallbladder cancer after Laparoscopy Cholecystectomy

El carcinoma de vesícula biliar es una entidad poco frecuente. El diagnóstico precoz de esta neoplasia es difícil, ya que sus síntomas son muy inespecíficos y muchas veces estes se realiza de manera tardía cuando el enfermo posee una enfermedad avanzada y solo para mitigar los síntomas. Con el crecimiento exponencial en el número de colecistectomías laparoscópicas en las últimas décadas, se ha generado un aumento en la detección de neoplasias incidentales, permitiendo ofrecer tratamiento curativo en un gran grupo de pacientes. Se evaluaron todas las colecistectomías realizadas durante julio de 2019 a diciembre de 2022 en el Hospital Nacional de Clínicas, Córdoba, Argentina. La evaluación patológica de todas las muestras quirúrgicas reveló una incidencia de 0,83% de adenocarcinoma insospechado en colecistectomías realizadas. 66% de los pacientes con neoplasias insospechadas pertenecían al sexo femenino

Gallbladder carcinoma is a rare entity. Early diagnosis of this neoplasia is difficult, since its symptoms are very unspecific and often this is done late when the patient has an advanced disease and only to mitigate symptoms. With the exponential growth in the number of laparoscopic cholecystectomies in recent decades, there has been an increase in the detection of incidental neoplasms, allowing offering curative treatment in a large group of patients. All cholecystectomies performed during July 2019 to December 2022 were evaluated at the National Hospital of Clinics, Córdoba, Argentina. Pathological evaluation of all surgical samples revealed an incidence of 0.83% of unsuspected adenocarcinoma in cholecystectomies performed. 66% of patients with unsuspected neoplasms were female

Melanoma of the gallbladder.

Melanoma is a highly malignant neoplasm with the most typical primary locations in the skin and eyeball and rarely reported in the other organs, including the gallbladder. More commonly metastases of melanoma of various primary sites to the gallbladder are observed. However, generally melanoma of the gallbladder is a rare entity with only 217 cases reported in the literature up to date. The paper summarizes knowledge on epidemiology, symptoms, laboratory and imaging findings, morphology, treatment options, and outcome of patients with both primary and metastatic melanoma to the gallbladder.

The Impact of a History of Different Other Cancers on the Long-Term Outcomes of Patients with Gallbladder Cancer: A Propensity Score-Adjusted, Population-Based Study.

BACKGROUND: As the number of cancer survivors increases, the prevalence of the second type of primary cancer will increase. In clinical trials, patients with a history of malignant tumors in the past are usually excluded. It is unknown whether previous cancers affect survival outcomes. The purpose of this study was to investigate the impact of previous malignant tumors on the long-term prognosis of patients with gallbladder cancer. METHODS: By using the Surveillance, Epidemiology and END Results (SEER) database, we collect patient data and obtain patients who had gallbladder cancer diagnosed in 2004-2015 and had an adaption and contrast 1:1 with cases. We applied the Kaplan-Meier analysis and Cox regression models to assess the influence of prior malignancy on gallbladder cancer survival outcomes. RESULTS: Among 8338 patients who had mainly gallbladder cancer, 525 (6.3%) suffered prior cancer. Prostate cancer (22.29%), Breast cancer (21.14%), and Genitourinary (14.67%) are the most common types. Before propensity score matching (PSM), two groups of different Kaplan-Meier curves were obtained by classifying previous cancer history, and by comparison, the all-cause difference in the group with previous cancer history was not salience (P = 0.31), but there is a protective effect on the Cancer-specific fatality rate (p < 0.001). Similar results were obtained after propensity score matching (PSM). Among the multivariate Cox analysis, previous malignancy had no obvious relation, including all causes (HR = 0.98, 95% CI: 0.86-1.12, p = 0.70) but a better gallbladder cancer-specific survival (HR =0.64, 95% CI: 0.55-0.75, P < 0.001). CONCLUSION: Prior cancer may not be an obvious factor impacting the survival of cancers of all-cause including the gallbladder. In clinical trials of gallbladder cancer, exclusion criteria based on cancer history should be assessed.

NCCN Guidelines® Insights: Biliary Tract Cancers, Version 2.2023.

In 2023, the NCCN Guidelines for Hepatobiliary Cancers were divided into 2 separate guidelines: Hepatocellular Carcinoma and Biliary Tract Cancers. The NCCN Guidelines for Biliary Tract Cancers provide recommendations for the evaluation and comprehensive care of patients with gallbladder cancer, intrahepatic cholangiocarcinoma, and extrahepatic cholangiocarcinoma. The multidisciplinary panel of experts meets at least on an annual basis to review requests from internal and external entities as well as to evaluate new data on current and emerging therapies. These Guidelines Insights focus on some of the recent updates to the NCCN Guidelines for Biliary Tract Cancers as well as the newly published section on principles of molecular testing.

Chemotherapy or chemotherapy followed by consolidation chemoradiation in postoperative (simple cholecystectomy) gall bladder cancer with residual disease, unsuitable for revision surgery? Risk stratification and outcomes.

Background: Revision surgery (RS) is the standard of care for gallbladder cancer (GBC) after simple cholecystectomy (SC). Often these patients are unsuitable for RS due to late referral or unresectable disease. Do such patients benefit with chemotherapy (CT) alone or dual-modality (CT followed by consolidation chemoradiotherapy [CTRT])? In the absence of any guidelines, we reviewed our data with CT or CTRT to inform us regarding adequate therapy. Materials and Methods: Patients of GBC post-SC referred to us (January 2008 to December 2016) were risk-stratified into three categories based on a diagnostic CT scan: No residual disease (NRD), limited volume residual disease (LR1: Residual/recurrent disease in GB bed with or without N1 nodal station involvement), advanced residual disease (LR2: Residual/recurrent disease involving GB bed with N2 nodal station involvement) and treated with CT or CT followed by CTRT. Response to therapy (RECIST), overall survival (OS), and adverse prognostic factors affecting OS were evaluated. Results: Out of 176 patients, 87were nonmetastatic (NRD = 17, LR1 = 33 and LR 2 = 37). 31 received CT, 49 CTRT and 8 defaulted. At a median follow up of 21 months, the median OS with CT versus consolidation CTRT was not reached in NRD (P = 0.57), 19 months versus 27 months in LR1 (P = 0.003) and 14 months versus 18 months in LR 2 (P = 0.29), respectively. On univariate analysis, residual disease burden, type of treatment (CT vs. CTRT), N stage, and response to treatment were found statistically significant. Conclusion: Our data suggest that CT followed by CTRT improves outcomes in patients with limited volume disease.

Preclinical evaluation of chimeric antigen receptor T cells targeting the carcinoembryonic antigen as a potential immunotherapy for gallbladder cancer.

Gallbladder cancer (GBC) is commonly diagnosed at late stages when conventional treatments achieve only modest clinical benefit. Therefore, effective treatments for advanced GBC are needed. In this context, the administration of T cells genetically engineered with chimeric antigen receptors (CAR) has shown remarkable results in hematological cancers and is being extensively studied for solid tumors. Interestingly, GBC tumors express canonical tumor-associated antigens, including the carcinoembryonic antigen (CEA). However, the potential of CEA as a relevant antigen in GBC to be targeted by CAR-T cell-based immunotherapy has not been addressed. Here we show that CEA was expressed in 88% of GBC tumors, with higher levels associated with advanced disease stages. CAR-T cells specifically recognized plate-bound CEA as evidenced by up-regulation of 4-1BB, CD69 and PD-1, and production of effector cytokines IFN-γ and TNF-α. In addition, CD8+ CAR-T cells up-regulated the cytotoxic molecules granzyme B and perforin. Interestingly, CAR-T cell activation occurred even in the presence of PD-L1. Consistent with these results, CAR-T cells efficiently recognized GBC cell lines expressing CEA and PD-L1, but not a CEA-negative cell line. Furthermore, CAR-T cells exhibited in vitro cytotoxicity and reduced in vivo tumor growth of GB-d1 cells. In summary, we demonstrate that CEA represents a relevant antigen for GBC that can be targeted by CAR-T cells at the preclinical level. This study warrants further development of the adoptive transfer of CEA-specific CAR-T cells as a potential immunotherapy for GBC.

Characteristics and outcomes of gallbladder cancer patients at the Tata Medical Center, Kolkata 2017-2019.

BACKGROUND: The north and north-eastern regions of India have among the highest incidence of gallbladder cancer (GBC) in the world. We report the clinicopathological charateristics and outcome of GBC patients in India. METHODS: Electronic medical records of patients diagnosed with GBC at Tata Medical Center, Kolkata between 2017 and 2019 were analyzed. RESULTS: There were 698 cases of confirmed GBC with a median age of 58 (IQR: 50-65) years and female:male ratio of 1.96. At presentation, 91% (496/544) had stage III/IV disease and 30% (189/640) had incidental GBC. The 2-year overall survival (OS) was 100% (95% CI: 100-100); 61% (95% CI: 45-83); 30% (95% CI: 21-43); and 9% (95% CI: 6-13) for stages I-IV, respectively (p = <0.0001).   For all patients, the 2-year OS in patients who had a radical cholecystectomy followed by adjuvant therapy (N = 36) was 50% (95% CI: 39-64), compared to 29% (95% CI: 22-38) for those who had a simple cholecystectomy and/or chemotherapy (N = 265) and 9% (95% CI: 6-14) in patients who were palliated (N = 107) (p = <0.0001). CONCLUSION: The combined surgical/chemotherapy approach for patients with stage II GBC showed the best outcomes. Early detection of GBC remains problematic with the majority of patients presenting with stage III-IV and who have a median survival of 9.1 months. Our data suggests that the tumor is chemoresponsive and multi-center collaborative clinical trials to identify alternative therapies are urgently required.

Update on immunotherapy in the management of gallbladder cancer.

Gallbladder cancer (GBC) is a relatively infrequent but highly lethal cancer with a poor prognosis. Management remains challenging and controversial, and most patients are diagnosed at an advanced stage. However, with the progressive advances in the use of immunotherapies, new treatment modalities are being implemented. In September 2022, the US FDA approved durvalumab (a PD-L1 inhibitor) in combination with chemotherapy for adult patients with locally advanced or metastatic GBC. This groundbreaking news is the first FDA approval for the use of immunotherapy in biliary tract cancers. This article reviews the newest advances and trials regarding immunotherapy for GBC.

Gallbladder cancer (GBC) is a malignant tumor that affects the cells of the gallbladder. Management of this condition is challenging and continuously evolving. Surgery, radiotherapy and chemotherapy are the current standards of care. However, recently, immunotherapy, a treatment that stimulates the host's immune system to target cancerous cells, has proven to be effective as a line of treatment. Promising results are continuously published. This article reviews the major advances in immunotherapy regarding the management of GBC.

A Gallbladder Cancer Survival Prediction Model Based on Multimodal Fusion Analysis.

BACKGROUND: Gallbladder cancer is the sixth most common malignant gastrointestinal tumor. Radical surgery is currently the only effective treatment, but patient prognosis is poor, with a 5-year survival rate of only 5-10%. Establishing an effective survival prediction model for gallbladder cancer patients is crucial for disease status assessment, early intervention, and individualized treatment approaches. The existing gallbladder cancer survival prediction model uses clinical data-radiotherapy and chemotherapy, pathology, and surgical scope-but fails to utilize laboratory examination and imaging data, limiting its prediction accuracy and preventing sufficient treatment plan guidance. AIMS: The aim of this work is to propose an accurate survival prediction model, based on the deep learning 3D-DenseNet network, integrated with multimodal medical data (enhanced CT imaging, laboratory test results, and data regarding systemic treatments). METHODS: Data were collected from 195 gallbladder cancer patients at two large tertiary hospitals in Shanghai. The 3D-DenseNet network extracted deep imaging features and constructed prognostic factors, from which a multimodal survival prediction model was established, based on the Cox regression model and incorporating patients' laboratory test and systemic treatment data. RESULTS: The model had a C-index of 0.787 in predicting patients' survival rate. Moreover, the area under the curve (AUC) of predicting patients' 1-, 3-, and 5-year survival rates reached 0.827, 0.865, and 0.926, respectively. CONCLUSIONS: Compared with the monomodal model based on deep imaging features and the tumor-node-metastasis (TNM) staging system-widely used in clinical practice-our model's prediction accuracy was greatly improved, aiding the prognostic assessment of gallbladder cancer patients.

A clinicoepidemiological and management profile of metastatic carcinoma gallbladder in the northeast part of Indian patients in a tertiary care center.

Introduction: Metastatic gallbladder cancer (GBC) is a highly fatal malignancy and it is difficult to treat the advanced stage of GBC. In India, northern and northeastern states are the worst affected by this disease. We, hereby, report the clinicoepidemiological and management profile of 242 patients of metastatic carcinoma of GB. Materials and Methods: In this study, a total of 242 cases of metastatic GBC (detected either on the first presentation or during follow-up) were managed at the Department of Medical Oncology tertiary care oncology center in the northeast part of India from May 2018 to September 2019. On presentation, all patients were subjected to detailed history and clinical examination, followed by requisite investigations and were treated as per the existent guidelines. Results: One-hundred and forty-two patients were female, while 100 patients were male out of 242 patients. Female patients with metastatic GBC presented with the mean age of 54, while for males, 51.4 years. The most common presentation was pain abdomen (81.8%), while the second most common was anorexia (77.2%), followed by weight loss (62.8%) and mass per abdomen (60.7%). The most common site of metastasis recorded in our study was the liver (79.7%), followed by nonregional abdominal lymph node (69.4%) and ascites (64.4%). Out of the 242 patients, 24 patients had presented in poor Eastern Cooperative Oncology Group Performance Status (≥3) hence were deemed unfit for any oncological interventions. About 136 (56.1%) patients had presented with features of obstructive jaundice, however only 108 patients were subjected to biliary drainage procedure. After the biliary drainage procedures, only one-third (38 out of 136; 35.1%) of patients were finally able to receive chemotherapy. Conclusion: In India, unfortunately, many patients present very late during the course of their illness. There is a need for the development of effective chemotherapy or targeted therapy and also there is an unmet need for patients' education. There has been an increase in the incidence of this malignancy, especially in the Northeast part of India; hence, it is the need of the hour to study various epidemiological and causative factors of the disease. Furthermore, the development of therapies for the effective management of this malignancy is really required.

Gallbladder cancer.

Gallbladder cancer (GBC) is the most common cancer of the biliary tract, characterized by a very poor prognosis when diagnosed at advanced stages owing to its aggressive behaviour and limited therapeutic options. Early detection at a curable stage remains challenging because patients rarely exhibit symptoms; indeed, most GBCs are discovered incidentally following cholecystectomy for symptomatic gallbladder stones. Long-standing chronic inflammation is an important driver of GBC, regardless of the lithiasic or non-lithiasic origin. Advances in omics technologies have provided a deeper understanding of GBC pathogenesis, uncovering mechanisms associated with inflammation-driven tumour initiation and progression. Surgical resection is the only treatment with curative intent for GBC but very few cases are suitable for resection and most adjuvant therapy has a very low response rate. Several unmet clinical needs require to be addressed to improve GBC management, including discovery and validation of reliable biomarkers for screening, therapy selection and prognosis. Standardization of preneoplastic and neoplastic lesion nomenclature, as well as surgical specimen processing and sampling, now provides reproducible and comparable research data that provide a basis for identifying and implementing early detection strategies and improving drug discovery. Advances in the understanding of next-generation sequencing, multidisciplinary care for GBC, neoadjuvant and adjuvant strategies, and novel systemic therapies including chemotherapy and immunotherapies are gradually changing the treatment paradigm and prognosis of this recalcitrant cancer.

Novel immune scoring dynamic nomograms based on B7-H3, B7-H4, and HHLA2: Potential prediction in survival and immunotherapeutic efficacy for gallbladder cancer.

Background: Gallbladder cancer (GBC) is a mortal malignancy with limited therapeutic strategies. We aimed to develop novel immune scoring systems focusing on B7-H3, B7-H4, and HHLA2. We further investigated their potential clinical effects in predicting survival and immunotherapeutic efficacy for GBC. Methods: This was a retrospective cohort study in a single center that explored the expression characteristics of B7-H3, B7-H4, and HHLA2. The immune scoring nomograms for prognostic were developed via logistic regression analyses. Their performance was evaluated using the Harrell concordance index (C-index) and decision curves analysis (DCA), and validated with calibration curves. Results: B7-H3, B7-H4, and HHLA2 manifested with a relatively high rate of co-expression patterns in GBC tissues. They were associated with worse clinicopathological stage, suppression of immune microenvironment, and unfavorable prognosis in postoperative survival. B7 stratification established based on B7-H3, B7-H4, and HHLA2 was an independent prognostic predictor (p<0.05 in both groups). Moreover, immune stratification was also successfully constructed based on B7 stratification and the density of CD8+ TILs (all p<0.001). The prediction models were developed based on B7-/or immune stratification combined with the TNM/or Nevin staging system. These novel models have excellent discrimination ability in predicting survival and immunotherapeutic efficacy for GBC patients by DCA and clinical impact plots. Finally, dynamic nomograms were developed for the most promising clinical prediction models (B7-TNM model and Immune-TNM model) to facilitate prediction. Conclusions: Immune scoring systems focusing on B7-H3, B7-H4, and HHLA2 may effectively stratify the prognosis of GBC. Prognostic nomograms based on novel immune scoring systems may potentially predict survival and immunotherapeutic efficacy in GBC. Further valid verification is necessary.