Tumor Burden and Immunotherapy: Impact on Immune Infiltration and Therapeutic Outcomes

Kim, Samuel I.; Cassella, Christopher R; Byrne, Katelyn T.

doi:10.3389/fimmu.2020.629722

Cited by 108 publications

(90 citation statements)

References 197 publications

(250 reference statements)

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“…However, additional studies are still warranted to refine the phenotype of cells expressing each inhibitory receptor combination and explore how to apply this fact into clinical intervention. Immune infiltration in TME is regarded as a crucial factor of immunotherapy response (3,36). Combined estimation of biomarkers independently predicting response has been betterstudied in recent decades.…”

Section: Discussionmentioning

confidence: 99%

Development of a Novel Immune Infiltration-Based Gene Signature to Predict Prognosis and Immunotherapy Response of Patients With Cervical Cancer

Zhang

et al. 2021

Front. Immunol.

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Predictive models could indicate the clinical outcome of patients with carcinoma. Cervical cancer is one of the most frequently diagnosed female malignancies. Herein, we proposed an immune infiltration-related gene signature that predicts prognosis of patients with cervical cancer and depicts the immune landscape as well. We utilized the transcriptome data of The Cancer Genome Atlas (TCGA) and estimated the infiltration level of 28 immune cell types. We screened out four immune cell types conducive to patient survival and recognized their shared differentially expressed genes (DEGs). Four core genes (CHIT1, GTSF1L, PLA2G2D, and GNG8) that composed the ultimate signature were identified via univariate and multivariate Cox regression. The optimal model we built up could distinguish patients with cervical cancer into high-score and low-score subgroups. These two subgroups showed disparity in aspects of patient survival, immune infiltration landscape, and response to immune checkpoint inhibitors. Additionally, we found that GTSF1L was decreased gradually along with the severity of cervical lesions, and its potential role in immune contexture and clinical practice were also demonstrated. Our results suggested that the Immunoscore based on four immune-related genes could serve as a supplementary criterion to effectively foresee the survival outcome, tumor infiltration status, and immunotherapy efficacy of cervical cancer patients.

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Section: Discussionmentioning

confidence: 99%

Development of a Novel Immune Infiltration-Based Gene Signature to Predict Prognosis and Immunotherapy Response of Patients With Cervical Cancer

Zhang

et al. 2021

Front. Immunol.

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“…Tumor burden (or tumor size) predicts response to immunotherapy in patients with cancer. A large TME and a small TME are characterized by different cell populations and responses to specific interventions [ 186 ]. Radiologic imaging such as computed tomographhy (CT) is the most commonly used technology for tumor burden monitoring even though it has limitations for the evaluation of the response to immunotherapy.…”

Section: Cxcl8 As a Prognosis Biomarker In Cancer Therapymentioning

confidence: 99%

Roles of the CXCL8-CXCR1/2 Axis in the Tumor Microenvironment and Immunotherapy

Han

Yang

et al. 2021

Molecules

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In humans, Interleukin-8 (IL-8 or CXCL8) is a granulocytic chemokine with multiple roles within the tumor microenvironment (TME), such as recruiting immunosuppressive cells to the tumor, increasing tumor angiogenesis, and promoting epithelial-to-mesenchymal transition (EMT). All of these effects of CXCL8 on individual cell types can result in cascading alterations to the TME. The changes in the TME components such as the cancer-associated fibroblasts (CAFs), the immune cells, the extracellular matrix, the blood vessels, or the lymphatic vessels further influence tumor progression and therapeutic resistance. Emerging roles of the microbiome in tumorigenesis or tumor progression revealed the intricate interactions between inflammatory response, dysbiosis, metabolites, CXCL8, immune cells, and the TME. Studies have shown that CXCL8 directly contributes to TME remodeling, cancer plasticity, and the development of resistance to both chemotherapy and immunotherapy. Further, clinical data demonstrate that CXCL8 could be an easily measurable prognostic biomarker in patients receiving immune checkpoint inhibitors. The blockade of the CXCL8-CXCR1/2 axis alone or in combination with other immunotherapy will be a promising strategy to improve antitumor efficacy. Herein, we review recent advances focusing on identifying the mechanisms between TME components and the CXCL8-CXCR1/2 axis for novel immunotherapy strategies.

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“…A possible explanation for the interaction of our new high/low-risk classification with irT effect on survival may be related to tumor burden. Several studies indicated that tumor burden and number of metastatic sites are negative predictive factors for immunotherapy efficacy [ 26 , 27 , 28 ]. It is suggested that the immune penetrance is lower when the tumor burden is high and that advanced tumors’ microenvironments have greater populations of immune suppressive cells [ 26 , 27 ].…”

Section: Discussionmentioning

confidence: 99%

Immune-Related Thyroiditis as a Predictor for Survival in Metastatic Renal Cell Carcinoma

Sagie

Gadot

Levartovsky

et al. 2022

Cancers

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Immune checkpoint inhibitors (CPI) are indicated for metastatic renal cell carcinoma (mRCC). Immune-related thyroiditis (irT), an immune-related adverse event (irAE), affects up to 30% of patients. We aimed to determine whether irT is associated with overall survival in mRCC. A retrospective cohort study of 123 consecutive patients treated with CPI for mRCC in a single center between 2015 and 2020 was conducted. Disease risk stratification was assessed by two methods: Heng criteria and a novel dichotomic stratification system to “Low risk” versus “High risk” adding number of metastatic sites. Thirty-eight percent of patients developed irT. In the general cohort, irT was not associated with a survival benefit. However, irT was associated with better survival in the poor risk group per Heng criteria (n = 17, HR = 0.25, p = 0.04) and in the novel “High risk” group (HR = 0.28, n = 42, p = 0.01), including after accounting for covariates in multivariate analysis (HR = 0.27, p = 0.003). Having any irAE was associated with improved survival in the whole cohort, with no significant correlation of any specific irAE, in either the whole cohort or the “High risk” group. We conclude that irT is an early and prevalent irAE, associated with prolonged survival in patients with poor/“High” risk mRCC.

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Tumor Burden and Immunotherapy: Impact on Immune Infiltration and Therapeutic Outcomes

Cited by 108 publications

References 197 publications

Development of a Novel Immune Infiltration-Based Gene Signature to Predict Prognosis and Immunotherapy Response of Patients With Cervical Cancer

Development of a Novel Immune Infiltration-Based Gene Signature to Predict Prognosis and Immunotherapy Response of Patients With Cervical Cancer

Roles of the CXCL8-CXCR1/2 Axis in the Tumor Microenvironment and Immunotherapy

Immune-Related Thyroiditis as a Predictor for Survival in Metastatic Renal Cell Carcinoma

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