An immune checkpoint score system for prognostic evaluation and adjuvant chemotherapy selection in gastric cancer

Wang, Jia-Bin; Li, Ping; Liu, Xiaolong; Zheng, Qi; Ma, Yu-Bin; Zhao, Yajun; Xie, Jian‐Wei; Ji, Lin; Lü, Jun; Chen, Qi‐Yue; Cao, Long‐Long; Ma, Lin; Liu, Lichao; Lian, Ning-Zi; Yang, Yinghong; Huang, Chang‐Ming; Zheng, Chao‐Hui

doi:10.1038/s41467-020-20260-7

Cited by 79 publications

(65 citation statements)

References 48 publications

(20 reference statements)

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“…For example, PD-1 and ICOS were strongly expressed on CD4 + T cells, whereas TIM-3 and VISTA were strongly expressed on macrophages. Furthermore, immunoregulatory protein expression was highly variable across CTCL patients, in line with previous reports ( 40 , 49 ); some patients had high expression of numerous markers whereas others had low expression of all markers. This degree of heterogeneity highlights the importance of analyzing functional immune molecules in individual patients and larger patient cohorts.…”

Section: Discussionsupporting

confidence: 91%

Highly Multiplexed Phenotyping of Immunoregulatory Proteins in the Tumor Microenvironment by CODEX Tissue Imaging

et al. 2021

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Immunotherapies are revolutionizing cancer treatment by boosting the natural ability of the immune system. In addition to antibodies against traditional checkpoint molecules or their ligands (i.e., CTLA-4, PD-1, and PD-L1), therapies targeting molecules such as ICOS, IDO-1, LAG-3, OX40, TIM-3, and VISTA are currently in clinical trials. To better inform clinical care and the design of therapeutic combination strategies, the co-expression of immunoregulatory proteins on individual immune cells within the tumor microenvironment must be robustly characterized. Highly multiplexed tissue imaging platforms, such as CO-Detection by indEXing (CODEX), are primed to meet this need by enabling >50 markers to be simultaneously analyzed in single-cells on formalin-fixed paraffin-embedded (FFPE) tissue sections. Assembly and validation of antibody panels is particularly challenging, with respect to the specificity of antigen detection and robustness of signal over background. Herein, we report the design, development, optimization, and application of a 56-marker CODEX antibody panel to eight cutaneous T cell lymphoma (CTCL) patient samples. This panel is comprised of structural, tumor, and immune cell markers, including eight immunoregulatory proteins that are approved or currently undergoing clinical trials as immunotherapy targets. Here we provide a resource to enable extensive high-dimensional, spatially resolved characterization of the tissue microenvironment across tumor types and imaging modalities. This framework provides researchers with a readily applicable blueprint to study tumor immunology, tissue architecture, and enable mechanistic insights into immunotherapeutic targets.

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Section: Discussionsupporting

confidence: 91%

Highly Multiplexed Phenotyping of Immunoregulatory Proteins in the Tumor Microenvironment by CODEX Tissue Imaging

et al. 2021

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“…patients (Cho et al, 2011;Cai et al, 2020Wang et al, 2020: Figure 4H). Therefore, we included PS-score as an effective indicator and other clinical characteristics, into Cox regression analysis and found that PS-score and stage were both two factors that independently affected the prognosis of GC patients (Table 2).…”

Section: Development and Validation Of A Gene Signature Based On Pyroptosis-related Clustersmentioning

confidence: 99%

The Pyroptosis-Related Signature Predicts Prognosis and Indicates Immune Microenvironment Infiltration in Gastric Cancer

Shao

Yang

et al. 2021

Front. Cell Dev. Biol.

149

145

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Gastric cancer (GC) is one of the leading causes of cancer-related deaths and shows high levels of heterogeneity. The development of a specific prognostic model is important if we are to improve treatment strategies. Pyroptosis can arise in response to H. pylori, a primary carcinogen, and also in response to chemotherapy drugs. However, the prognostic evaluation of GC to pyroptosis is insufficient. Consensus clustering by pyroptosis-related regulators was used to classify 618 patients with GC from four GEO cohorts. Following Cox regression with differentially expressed genes, our prognosis model (PS-score) was built by LASSO-Cox analysis. The TCGA-STAD cohort was used as the validation set. ESTIMATE, CIBERSORTx, and EPIC were used to investigate the tumor microenvironment (TME). Immunotherapy cohorts by blocking PD1/PD-L1 were used to investigate the treatment response. The subtyping of GC based on pyroptosis-related regulators was able to classify patients according to different clinical traits and TME. The difference between the two subtypes identified in this study was used to develop a prognosis model which we named “PS-score.” The PS-score could predict the prognosis of patients with GC and his/her overall survival time. A low PS-score implies greater inflammatory cell infiltration and better response of immunotherapy by PD1/PD-L1 blockers. Our findings provide a foundation for future research targeting pyroptosis and its immune microenvironment to improve prognosis and responses to immunotherapy.

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“…Despite this amount of data, results are still confounding. Baseline PNI (prognostic nutritional Index), for example, has been reported as useful in some retrospective studies [ 66 ], but questioned [ 67 ] or not confirmed in others [ 68 ]. In melanoma patients, overweight or obese patients may derive benefit in terms of progression-free survival (PFS), but not in overall survival (OS).…”

Section: Nutritional Care During Immunotherapy: Does the Boundless Prairie Have A Fence?mentioning

confidence: 99%

The Clinical Value of Nutritional Care before and during Active Cancer Treatment

Aprile¹,

Basile²,

Giaretta³

et al. 2021

Nutrients

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Malnutrition and muscle wasting are frequently reported in cancer patients, either linked to the tumor itself or caused by oncologic therapies. Understanding the value of nutritional care during cancer treatment remains crucial. In fact, cancer-associated sarcopenia plays a key role in determining higher rates of morbidity, mortality, treatment-induced toxicities, prolonged hospitalizations and reduced adherence to anticancer treatment, worsening quality of life and survival. Planning baseline screening to intercept nutritional troubles earlier, organizing timely reassessments, and providing adequate counselling and dietary support, healthcare professional may positively interfere with this process and improve patients’ overall outcomes during the whole disease course. Several screening tools have been proposed for this purpose. Nutritional Risk Screening (NRS), Mini Nutritional Assessment (MNA), Patient Generated Subjective Global Assessment (PG-SGA) are the most common studied. Interestingly, second-level tools including skeletal muscle index (SMI) and bioelectric impedance analysis (BIA) provide a more precise assessment of body composition, even if they are more complex. However, nutritional assessment is not currently used in clinical practice and procedures must be standardized in order to improve the efficacy of standard chemotherapy, targeted agents or even checkpoint inhibitors that is potentially linked with the patients’ nutritional status. In the present review, we will discuss about malnutrition and the importance of an early nutritional assessment during chemotherapy and treatment with novel checkpoint inhibitors, in order to prevent treatment-induced toxicities and to improve survival outcomes.

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An immune checkpoint score system for prognostic evaluation and adjuvant chemotherapy selection in gastric cancer

Cited by 79 publications

References 48 publications

Highly Multiplexed Phenotyping of Immunoregulatory Proteins in the Tumor Microenvironment by CODEX Tissue Imaging

Highly Multiplexed Phenotyping of Immunoregulatory Proteins in the Tumor Microenvironment by CODEX Tissue Imaging

The Pyroptosis-Related Signature Predicts Prognosis and Indicates Immune Microenvironment Infiltration in Gastric Cancer

The Clinical Value of Nutritional Care before and during Active Cancer Treatment

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