Pericardial disease in patients treated with immune checkpoint inhibitors

BackgroundThere are limited data on the occurrence, associations and outcomes of pericardial effusions and pericarditis on or after treatment with immune checkpoint inhibitors (ICIs).MethodsThis was a retrospective study at a single academic center that compared 2842 consecutive patients who received ICIs with 2699 age- and cancer-type matched patients with metastatic disease who did not receive ICI. A pericardial event was defined as a composite outcome of pericarditis and new or worsening moderate or large pericardial effusion. The endpoints were obtained through chart review and were blindly adjudicated. To identify risk factors associated with a pericardial event, we compared patients who developed an event on an ICI with patients treated with an ICI who did not develop a pericardial event. Cox proportional-hazard model and logistical regression analysis were performed to study the association between ICI use and pericardial disease as well as pericardial disease and mortality. An additional 6-week landmark analysis was performed to account for lead-time bias.ResultsThere were 42 pericardial events in the patients treated with ICI (n=2842) over 193 days (IQR: 64–411), yielding an incidence rate of 1.57 events per 100 person-years. There was a more than fourfold increase in risk of pericarditis or a pericardial effusion among patients on an ICI compared with controls not treated with ICI after adjusting for potential confounders (HR 4.37, 95% CI 2.09 to 9.14, p<0.001). Patients who developed pericardial disease while on an ICI had a trend for increased all-cause mortality compared with patients who did not develop a pericardial event (HR 1.53, 95% CI 0.99 to 2.36, p=0.05). When comparing those who developed pericardial disease after ICI treatment with those who did not, a higher dose of corticosteroid pre-ICI (>0.7 mg/kg prednisone) was associated with increased risk of pericardial disease (HR 2.56, 95% CI 1.00 to 6.57, p=0.049).ConclusionsICI use was associated with an increased risk of development of pericardial disease among patients with cancer and a pericardial event on an ICI was associated with a trend towards increase in mortality.

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SAT-411 Vitamin D Levels and Risk of Thyroid Immune Related Adverse Events in Patients on Immune Checkpoint Inhibitors

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.598 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Samantha Kass Newman ◽

Amanda C Leiter ◽

Emily Carroll ◽

Brooks C Danielle ◽

Jennifer Ben Shimol ◽

...

Keyword(s):

Vitamin D ◽

Adverse Events ◽

Cell Carcinoma ◽

Immune Checkpoint ◽

Thyroid Disease ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Cancer Type ◽

Increased Risk ◽

Cancer Types

Abstract Immune checkpoint inhibitors (ICI), such as monoclonal antibodies to cytotoxic T lymphocyte associated protein 4 (CTLA-4), programmed cell death 1 (PD-1) and PD ligand 1 (PD-L1) are recognized as effective cancer-directed therapies. Yet, ICI-induced activation of the immune system results in immune-related adverse events (irAEs) affecting many organs, including the thyroid. Separately, Vitamin D (Vit D) deficiency has been associated with increased risk of autoimmune thyroid disease. We hypothesized that patients who were Vit D deficient at the time of initiating ICI therapy would be more likely to develop thyroid irAEs. We retrospectively collected data for 411 patients who received ICIs at our institution between January 2011 and April 2017. We then identified 91 of these patients who had 25-OH Vit D levels obtained; 2 were excluded from analysis due to previous thyroidectomy. We recorded demographics, cancer type, Vit D level closest to the start date of ICI therapy, and thyroid irAEs. Patients were categorized as Vit D deficient (<20ng/mL), insufficient (20-29.9ng/mL) or sufficient (≥30ng/mL). We compared patient demographic and clinical characteristics between the VitD categories. Proportions were compared using Fisher’s Exact Test. Of the 89 patients, 48.3% were female and 51.7% were male. Mean age was 67.2 (SD±10.6) years with 57% white, 8% black, 10% hispanic, 7% Asian, and 18% other / unknown. 20% of patients had non-small cell lung cancer, 15% melanoma, 13% hepatocellular carcinoma, 12% multiple myeloma (MM), 8% renal cell carcinoma (RCC), 7% head and neck squamous cell carcinoma, 7% urothelial carcinoma and 18% other cancer types. 21.3% were Vit D deficient, 40.4% were insufficient, and 38.2% were sufficient. Patients with Vit D deficiency and insufficiency were younger (age 64.1± 11.7, 65.9±9.5 years, respectively) than the Vit D sufficiency group (70.1±10.5years, p=0.046). No significant differences between males and females were observed between Vit D categories. Across cancer types, the highest prevalence of Vit D deficiency was in RCC (42.9%) and MM (36.4%). Hispanic and Asian patients had the highest prevalence of Vit D deficiency (44.4% and 33.3%, respectively). 11 patients (12.4%) developed a thyroid irAE. Thyroid irAEs occurred in 5.3% with Vit D deficiency, 8.1% with Vit D insufficiency, and 20% with Vit D sufficiency, but the association was not statistically significant (p=0.2). In contrast to our hypothesis, Vit D deficiency was not associated with a higher rate of thyroid irAEs. In fact our data suggest that patients who are vitamin D sufficient at the time of starting ICI therapy may be at greater risk of developing thyroid irAEs. Our study is limited by small numbers and the retrospective nature of the study. Prospective studies should be performed to determine the significance of Vit D levels on ICI related thyroid disease.

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From Oncogenic Signaling Pathways to Single-Cell Sequencing of Immune Cells: Changing the Landscape of Cancer Immunotherapy

Molecules ◽

10.3390/molecules26082278 ◽

2021 ◽

Vol 26 (8) ◽

pp. 2278

Author(s):

Afshin Derakhshani ◽

Zeinab Rostami ◽

Hossein Safarpour ◽

Mahdi Abdoli Shadbad ◽

Niloufar Sadat Nourbakhsh ◽

...

Keyword(s):

Single Cell ◽

Signaling Pathways ◽

Immune Cells ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Cancer Development ◽

Immune Checkpoints ◽

Single Cell Sequencing ◽

Increased Risk

Over the past decade, there have been remarkable advances in understanding the signaling pathways involved in cancer development. It is well-established that cancer is caused by the dysregulation of cellular pathways involved in proliferation, cell cycle, apoptosis, cell metabolism, migration, cell polarity, and differentiation. Besides, growing evidence indicates that extracellular matrix signaling, cell surface proteoglycans, and angiogenesis can contribute to cancer development. Given the genetic instability and vast intra-tumoral heterogeneity revealed by the single-cell sequencing of tumoral cells, the current approaches cannot eliminate the mutating cancer cells. Besides, the polyclonal expansion of tumor-infiltrated lymphocytes in response to tumoral neoantigens cannot elicit anti-tumoral immune responses due to the immunosuppressive tumor microenvironment. Nevertheless, the data from the single-cell sequencing of immune cells can provide valuable insights regarding the expression of inhibitory immune checkpoints/related signaling factors in immune cells, which can be used to select immune checkpoint inhibitors and adjust their dosage. Indeed, the integration of the data obtained from the single-cell sequencing of immune cells with immune checkpoint inhibitors can increase the response rate of immune checkpoint inhibitors, decrease the immune-related adverse events, and facilitate tumoral cell elimination. This study aims to review key pathways involved in tumor development and shed light on single-cell sequencing. It also intends to address the shortcomings of immune checkpoint inhibitors, i.e., their varied response rates among cancer patients and increased risk of autoimmunity development, via applying the data from the single-cell sequencing of immune cells.

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Abstract 15395: Immune Checkpoint Inhibitors for Cancer Are Associated With Increased Venous Thromboembolism Events

Circulation ◽

10.1161/circ.142.suppl_3.15395 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Jingyi Gong ◽

Zsofia Drobni ◽

Raza Alvi ◽

Sean Murphy ◽

Sarah Hartmann ◽

...

Keyword(s):

Venous Thromboembolism ◽

Immune Activation ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Massachusetts General Hospital ◽

Control Period ◽

Fold Increase ◽

Vein Thrombosis ◽

Increased Risk

Introduction: Immune checkpoint inhibitors (ICI) lead to immune activation, increased inflammation and cancer cell death. Both immune activation and inflammation are critical pathobiological drivers for venous thromboembolism (VTE). There are no robust data testing the effect of ICIs on the risk of developing VTE. Methods: This is a retrospective study of 2854 patients who received ICIs at Massachusetts General Hospital, Boston, MA. VTE events, defined as a composite of deep vein thrombosis (DVT) or pulmonary embolism (PE), were identified by individual chart review and were blindly adjudicated using standard criteria. A case-crossover design was applied with an “at-risk period” defined as the two-year period after and the “control period” as the two years prior to treatment. Incidence rate ratio (IRR) was calculated using Poisson’s regression. Results: Immune checkpoint inhibitor use increased VTE risk by 1.84-fold from 4.85 per 100-person years to 8.91 per 100 person-years (IRR 1.84, 95% confidence interval: 1.54 - 2.19, p <0.001). Of the individual components, there was a 2.44-fold increase in DVT risk (2.30 to 5.58 per 100 person-years) and 1.68-fold increase in PE risk (2.96 to 5.00 per 100 person-years). Comparing patients with and without a VTE event, those with a VTE event after ICI initiation had a higher rate of prior VTE, lung cancer, urothelial cancer, and a higher platelet count and white blood cell count at baseline. At 6 months post ICI initiation, 165 (8.6%) patients had a VTE event and of these patients 136 (7.1%) had no prior VTE. Conclusions: Patients with cancer treated with ICIs are at increased risk of developing VTE. Whether prophylaxis for VTE among patients starting an ICI reduces this risk is unclear.

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Risk factors for myocarditis associated with immune checkpoint inhibitors using real-world clinical data.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e15100 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e15100-e15100 ◽

Cited By ~ 1

Author(s):

Prantesh Jain ◽

Jahir Gutierrez Bugarin ◽

Avirup Guha ◽

Chhavi Jain ◽

Tingke Shen ◽

...

Keyword(s):

Risk Factors ◽

Liver Disease ◽

Cancer Patients ◽

Real World ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Cox Proportional Hazards ◽

Cancer Type ◽

Real World Data

e15100 Background: Immune checkpoint inhibitors (ICIs) can cause unique, high-grade immune-related adverse events. Although rare, ICI related myocarditis has the highest fatality rate (~50%). Cardiovascular monitoring is not routinely performed in patients on ICI treatment, thus risk factors remain unknown. Characterizing rare but fatal cardiac toxicities requires integration of real-world data. Methods: U.S claims data (IBM MarketScan) of over 30 million commercially insured individuals was leveraged to identify 2,687,301 cancer patients between 2011-2018. Patients ≥18 years of age treated with ICIs (targeting CTLA4 (ipilimumab) and/or the PD1 (nivolumab, pembrolizumab)/PDL1 (atezolizumab, avelumab, durvalumab) alone or in combination with ICI and/or chemotherapy were identified and followed until disenrollment. Myocarditis, comorbidities, and treatment details were identified using diagnosis and billing codes. Analyses included descriptive statistics and Cox proportional hazards regression. Results: 16,541 ICI treated cancer patients were included (median age 60; 58% male). Myocarditis was identified in 252 (1.5%) patients, majority (90%) ≥50 years old (median 63) with 12,040 person-years of follow up. 62% received anti-PD1 monotherapy, 12% anti-CTLA4, and 15% received combination treatment with other ICIs and/or chemotherapy. Most common cancer types were lung (48%), melanoma (25%), and renal cancer (14%). Cumulative incidence of myocarditis at 1 year was 2.06%; 95% CI (1.78-2.37), median onset of 80.5 days, 42% occurring within 60 days of treatment. By univariate analyses, age, cancer type, diabetes (DM), hypertension (HTN), kidney, liver disease, atrial fibrillation (AF) were related to myocarditis. Risk was lower in patients who received anti-CTLA4 monotherapy (HR: 0.490; 95% CI: 0.26-0.92; p = 0.0251). On multivariable regression analyses only age, cancer type (renal, lung cancer), comorbidities DM and liver disease were significantly associated with myocarditis (Table). Conclusions: This is the largest real-world longitudinal study for ICI associated myocarditis showing higher than reported incidence and identifiable risk factors. [Table: see text]

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Antibiotics Treatment and Immune-checkpoint Inhibitors Efficacy: A Systematic Review and Meta-analysis

10.21203/rs.3.rs-30778/v1 ◽

2020 ◽

Author(s):

Jie Hao ◽

Yang Zhao ◽

Jiangyi He ◽

Yunlong Wang ◽

Yan Dong

Keyword(s):

Prognostic Factor ◽

Advanced Cancer ◽

Immune Checkpoint ◽

Fixed Effects ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Meta Analysis ◽

Time Interval ◽

Prognostic Information ◽

Increased Risk

Abstract Background: Immune-checkpoint inhibitors (ICIs) have been approved as 1st line therapy and benefit patients with advanced cancer. However, still many patients fail to achieve the significant efficacy, a predictor for precise patient selection is needed. The aim of our study is to determine whether the administration of antibiotics before or at the beginning of ICIs treatment is a prognostic factor of progression-free survival (PFS) and overall survival (OS) in patients with advanced cancer.Methods: A systematic search in PubMed, Embase, Cochrane and Web of Science databases was conducted using the search terms antibiotic, PD-1, PD-L1, CTLA-4, combined with cancer, tumor, neoplasm, or carcinoma. Data extraction was performed independently. Hazard ratio (HR) for PFS and OS of antibiotics (+) group vs antibiotics (-) group were pooled according to random or fixed-effects models. HRs with 95% confidence intervals (CIs) for PFS and OS were pooled to obtain prognostic information and aggregate values.Results: Nine studies including 1163 patients were included in this meta-analysis. By PFS analysis, antibiotics administration was associated with a significantly increased risk of disease progression (HR, 1.76; 95% CI, 1.37-2.26; P< 0.01). By OS analysis, antibiotics uptake also showed an HR in favor of death (HR, 1.7; 95% CI, 1.40-2.07; P< 0.01).Conclusions: Based on the existing evidence, antibiotics administration is a prognostic factor for reduced PFS and OS in patients receiving ICIs treatment. The time interval between antibiotics administration and ICIs treatment should be considered.

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Case Report: Cardiac Toxicity Associated With Immune Checkpoint Inhibitors

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.727445 ◽

2021 ◽

Vol 8 ◽

Author(s):

Ru Chen ◽

Ling Peng ◽

Zhihua Qiu ◽

Yan Wang ◽

Fen Wei ◽

...

Keyword(s):

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Troponin I ◽

Systemic Corticosteroid ◽

Checkpoint Inhibitors ◽

Cardiac Conduction ◽

Fulminant Myocarditis ◽

Cancer Type ◽

Life Threatening ◽

The Subject

Immune checkpoint inhibitors (ICIs) have now emerged as a mainstay of treatment for various cancer. Along with the development of ICIs, immune-related adverse effects (irAEs) have been the subject of wide attention. The cardiac irAE, a rare but potentially fatal and fulminant effect, have been reported recently. This article retrospectively reviewed 10 cases from our hospital with cardiac irAEs, with severity ranging from asymptomatic troponin-I elevations to cardiac conduction abnormalities and even fulminant myocarditis. In our series, all the cases were solid tumors and lung cancer was the most frequent cancer type (4,40%). In total, three (30.0%) patients experienced more than one type of life-threatening complication. A systemic corticosteroid was given to nine patients (90.0%). The majority of cases (7, 70%) were performed at an initial dose of 1–2 mg/kg/day. Two (20.0%) patients were admitted to ICU, three (30.0%) patients were put on mechanical ventilation, two (20.0%) patients received the plasma exchange therapy, and one patient was implanted with a pacemaker. Two (20.0%) of the patients succumbed and died, with a median duration of 7.5 days (IQR5.0–10.0) from diagnosis of cardiac irAE to death. Based on these results, we recommend that clinicians be alert to cardiac irAEs, including performing cardiovascular examinations before ICI treatment to accurately diagnose suspected myocarditis, enabling immediate initiation of immunosuppressive therapy to improve prognosis.

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Risk of tuberculosis in patients with cancer treated with immune checkpoint inhibitors: a nationwide observational study

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2021-002960 ◽

2021 ◽

Vol 9 (9) ◽

pp. e002960

Author(s):

Seongman Bae ◽

Ye-Jee Kim ◽

Min-ju Kim ◽

Jwa Hoon Kim ◽

Sung-Cheol Yun ◽

...

Keyword(s):

Incidence Rate ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Cox Regression ◽

Checkpoint Inhibitors ◽

Exposure Group ◽

Patients With Cancer ◽

Increased Risk ◽

Insurance Claims Data ◽

Health Insurance Claims Data

BackgroundWhile some recent studies have reported the development of tuberculosis (TB) in patients exposed to immune checkpoint inhibitors (ICIs), there is limited evidence to date. Therefore, we evaluated the risk of TB in patients with cancer exposed to ICIs using the National Health Insurance claims data in South Korea.MethodsPatients with diagnostic codes for non-small cell lung cancer, urothelial carcinoma or melanoma between August 2017 and June 2019 were identified. The incidence rate and standardized incidence ratio (SIR) of TB were calculated for both the ICI exposure and non-exposure groups. The risk of TB according to ICI exposure was assessed using a multivariable Cox regression model.ResultsDuring the study period, 141 550 patients with cancer and 916 new TB cases were identified. Among the 5037 patients exposed to ICIs, 20 were diagnosed with TB at a median of 2.2 months after the ICI was initiated. The crude incidence rate of TB per 100,000 person-years was 675.8 (95% CI 412.8 to 1043.8) for the ICI exposure group and 599.1 (95% CI 560.5 to 639.6) for the non-exposure group. The SIR for TB was 8.1 (95% CI 8.0 to 8.2) in the ICI exposure group. After adjusting for potential confounding factors, ICI treatment was not significantly associated with an increased risk of TB (HR: 0.73; 95% CI 0.47 to 1.14).ConclusionsWhile the incidence of TB in cancer patients exposed to ICIs was eightfold higher than in the general population, the risk of patients with cancer developing TB did not significantly differ according to ICI exposure.

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Cardiotoxicity associated with immune checkpoint inhibitors: A retrospective analysis of patients at an academic tertiary care center

10.21203/rs.3.rs-50662/v2 ◽

2020 ◽

Author(s):

Nida Waheed ◽

Michael G. Fradley ◽

David DeRemer ◽

Ahmad Mahmoud ◽

Chintan P. Shah ◽

...

Keyword(s):

Heart Failure ◽

Anticancer Agents ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Care Center ◽

Tertiary Care ◽

Data Repository ◽

Tertiary Care Center ◽

Pericardial Disease

Abstract Background Immune checkpoint inhibitors (ICIs) are a novel class of anticancer agents that have demonstrated clinical response for both solid and hematological malignancies. ICIs are associated with development of immune-related adverse events including cardiotoxicity. We estimated the incidence of ICI-related cardiotoxicity in patients treated with ICIs at a large, tertiary care center. Methods All patients with a cancer diagnosis who received any ICI treatment in the University of Florida’s Integrated Data Repository from 2011-2017 were included. Cardiotoxicity was defined as a new ICD diagnosis code for cardiomyopathy, heart failure, arrhythmia, heart block, pericardial disease, or myocarditis after initiation of ICI treatment. Results Of 102,701 patients with a diagnosis of malignancy, 424 patients received at least one ICI. Sixty-two (14.6%) patients were diagnosed with at least one possible form of cardiotoxicity after initiation of ICI therapy. Of the 374 patients receiving one ICI, 21 (5.6%) developed heart failure. Of the 49 patients who received two ICIs sequentially, three (6.1%) developed heart failure and/or cardiomyopathy. Cardiotoxicity was diagnosed at a median of 63 days after initial ICI exposure. One patient developed myocarditis 28 days after receiving nivolumab. Mortality in those who developed ICI-attributable cardiotoxicity was higher compared to those who did not (66.1% vs. 41.4%, odds ratio=2.77, 1.55-4.95, p=0.0006). Conclusions This study suggests that the incidence of ICI-related cardiotoxicity may be higher than previously reported.

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Association between the type of thyroid dysfunction induced by immune checkpoint inhibitors and prognosis in cancer patients

10.21203/rs.3.rs-841797/v1 ◽

2021 ◽

Author(s):

Han-sang Baek ◽

Chaiho Jeong ◽

Kabsoo Shin ◽

Jaejun Lee ◽

Dong-Jun Lim ◽

...

Keyword(s):

Subclinical Hypothyroidism ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Thyroid Dysfunction ◽

Checkpoint Inhibitors ◽

Hazard Ratio ◽

Cancer Type ◽

Significant Difference ◽

The Difference ◽

Lower Hazard

Abstract Background Immune checkpoint inhibitors (ICIs) cause thyroid immune-related adverse effects (irAEs). However, associations between each type of thyroid immune-related adverse effect (irAE) and the anti-tumor effect of ICI remains unknown. This study aimed to determine the effects of each type of thyroid dysfunction on patient survival. Methods Patients who initiated ICI treatment from January 2015 to December 2019 in Seoul St. Mary’s Hospital were retrospectively analyzed. Thyroid dysfunction was classified into four types: newly developed overt or subclinical hypothyroidism, thyrotoxicosis, worsened hypothyroidism, and subclinical hyperthyroidism. Patients were divided into two groups according to the presence or absence of thyroid dysfunction. Results Among the 196 patients, 66 (33.7%) developed thyroid irAEs. There was no significant difference in age, sex, or cancer type between the two groups. The overall survival in patients with thyroid irAEs was significantly higher than that in patients without thyroid irAEs (38 months vs. 13 months, respectively, p = 0.005). After adjusting for confounding factors, the hazard ratio for mortality in the thyroid irAE group compared to the no thyroid irAE group was 0.520 (p = 0.007). Newly developed overt or subclinical hypothyroidism patients showed a significantly lower hazard ratio for morbidity of 0.309 (p = 0.001). Patients with thyrotoxicosis showed a worse hazard ratio for morbidity than those without thyroid irAE, although the difference was not statistically significant. Conclusions It was verified that ICI treatment-induced thyroid dysfunction was associated with better survival, even in the real-world practice. Thus, endocrinologists should cooperate with oncologists to monitor patients treated with ICIs.

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Chromosomal Instability May Not Be a Predictor for Immune Checkpoint Inhibitors from a Comprehensive Bioinformatics Analysis

Life ◽

10.3390/life10110276 ◽

2020 ◽

Vol 10 (11) ◽

pp. 276

Author(s):

Chiao-En Wu ◽

Da-Wei Yeh ◽

Yi-Ru Pan ◽

Wen-Kuan Huang ◽

Ming-Huang Chen ◽

...

Keyword(s):

Immune Checkpoint ◽

Predictive Value ◽

Chromosomal Instability ◽

Immune Checkpoint Inhibitors ◽

Bioinformatics Analysis ◽

Checkpoint Inhibitors ◽

P Value ◽

Cancer Type ◽

Significant Difference ◽

The Impact

Immune checkpoint inhibitors (ICIs) have become the standard of care in various cancers, although their predictive tools have not yet completely developed. Here, we aimed to exam the role of 70-gene chromosomal instability signature (CIN70) in cancers, and its association with previous predictors, tumor mutation burden (TMB), and microsatellite instability (MSI), for patients undergoing ICIs, as well as the possible predictive value for ICIs. We examined the association of CIN70 with TMB and MSI, as well as the impact of these biomarkers on the survival of 33 cancer cohorts from The Cancer Genome Atlas (TCGA) databank. The predictive value of the ICIs of CIN70 in previously published reports was also validated. Using the TCGA dataset, CIN70 scores were frequently (either positively or negatively) associated with TMB, but were only significantly associated with MSI status in three types of cancer. In addition, our current study showed that all TMB, MSI, and CIN70 had their own prognostic values for survival in patients with various cancers, and that they could be cancer type-specific. In two validation cohorts (melanoma by Hugo et al. and urothelial cancer by Snyder et al.), no significant difference of CIN70 scores was found between responders and non-responders (p-value = 0.226 and 0.108, respectively). In addition, no overall survival difference was noted between patients with a high CIN70 and those with a low CIN70 (p-value = 0.106 and 0.222, respectively). In conclusion, the current study, through a comprehensive bioinformatics analysis, demonstrated a correlation between CIN70 and TMB, but CIN70 is not the predictor for cancer patients undergoing ICIs. Future prospective studies are warranted to validate these findings.

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