Multimarker scores of Th1 and Th2 immune cellular profiles in peripheral blood predict response and immune related toxicity with CTLA4 blockade and IFNα in melanoma

Khunger, Arjun; Sarikonda, Ghanashyam; Tsau, Jennifer; Pahuja, Anil; Alfonso, Zeni; Gao, Jane; Laing, Christian; Vaupel, Christine; Dakappagari, Naveen; Tarhini, Ahmad A.

doi:10.1016/j.tranon.2021.101014

Cited by 14 publications

(10 citation statements)

References 51 publications

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“…31 Similarly, there is an ongoing interest in the development of on-treatment prognostic biomarkers such as the monitoring of circulating tumor cells utilizing liquid biopsies for response to treatment and early detection of disease progression. 52,53 To further dissect the molecular pathways and TME in the responders and non-responders to ICIs, we performed gene set enrichment analyses in these cohorts. Similar to the predictive gene signatures results, we observed that the tumors of ICI responders were enriched with genes related to interferon-γ, inflammation, and immune activation.…”

Section: Discussionmentioning

confidence: 99%

“…They demonstrated that the on‐treatment pathway‐based signatures were more predictive than the pretreatment pathway‐based signatures in predicting response to ICIs in melanoma 31 . Similarly, there is an ongoing interest in the development of on‐treatment prognostic biomarkers such as the monitoring of circulating tumor cells utilizing liquid biopsies for response to treatment and early detection of disease progression 52,53 …”

Section: Discussionmentioning

confidence: 99%

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Systematic evaluation of the predictive gene expression signatures of immune checkpoint inhibitors in metastatic melanoma

Coleman

Xie

Tarhini

et al. 2022

Molecular Carcinogenesis

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Advances in immunotherapy, including immune checkpoint inhibitors (ICIs), have transformed the standard of care for many types of cancer including melanoma. ICIs have improved the overall outcome of melanoma patients; however, a significant proportion of patients suffer from primary or secondary tumor resistance. Therefore, there is an urgent need to develop predictive biomarkers to better select patients for ICI therapy. Numerous biomarkers that predict the response of melanoma to ICIs have been investigated, including biomarker signatures based on genomics or transcriptomics. Most of these predictive biomarkers have not been systematically evaluated across different cohorts to determine the reproducibility of these signatures in metastatic melanoma. We evaluated 28 previously published predictive biomarkers of ICIs based on gene expression signatures in eight previously published studies with available RNA‐sequencing data in public repositories. We found that signatures related to IFN‐γ‐responsive genes, T and B cell markers, and chemokines in the tumor immune microenvironment are generally predictive of response to ICIs in these patients. In addition, we identified that these predictive biomarkers have higher predictive values in on‐treatment samples as compared to pretreatment samples in metastatic melanoma. The most frequently overlapping genes among the top 18 predictive signatures were CXCL10, CXCL9, PRF1, RANTES, IFNG, HLA‐DRA, GZMB, and CD8A. From gene set enrichment analysis and cell type deconvolution, we estimated that the tumors of responders were enriched with infiltrating cytotoxic T‐cells and other immune cells and the upregulation of genes related to interferon‐γ signaling. Conversely, the tumors of non‐responders were enriched with stromal‐related cell types such as fibroblasts and myofibroblasts, as well as enrichment with T helper 17 cell types across all cohorts. In summary, our approach of validating and integrating multi‐omics data can help guide future biomarker development in the field of ICIs and serve the quest for a more personalized therapeutic approach for melanoma patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Systematic evaluation of the predictive gene expression signatures of immune checkpoint inhibitors in metastatic melanoma

Coleman

Xie

Tarhini

et al. 2022

Molecular Carcinogenesis

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“…118 Previous evidence revealed that higher level of baseline Th1 cells in peripheral blood was associated with preoperative radiological response, whereas higher Th2 cells were correlated with progressive disease in melanoma patients who were treated with ipilimumab in combination with high-dose IFN-a as neoadjuvant therapy. 119 Nevertheless, in breast cancer, Th2 cells were found to be associated with better prognosis. 120 EGFR tumors were reported to have less infiltrated Th2 cells.…”

Section: Other Immune Cellsmentioning

confidence: 99%

Immune Checkpoint Inhibitors in EGFR-Mutated NSCLC: Dusk or Dawn?

Qiao

Jiang

Liu

et al. 2021

Journal of Thoracic Oncology

100

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“…Several studies have reported a positive association between the incidence of irAEs and the survival outcomes ( 6 , 61 , 62 ), while others have found no such association ( 63 ). A systematic review and meta-analysis has shown that grade ≥3 toxicities were correlated with a better overall response rate, but poor overall survival ( 64 ), while another has linked irAEs with better survival and response ( 7 ).…”

Section: Toxicity Itself As a Biomarkermentioning

confidence: 99%

Predictive Biomarkers of Severe Immune-Related Adverse Events With Immune Checkpoint Inhibitors: Prevention, Underlying Causes, Intensity, and Consequences

Gutiérrez

Barahona²

2022

Front. Med.

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Immune checkpoint inhibitors (ICIs) have dramatically transformed oncology by prolonging overall survival and yielding better patient tolerance compared to other chemotherapeutic agents. However, numerous questions remain unanswered about the toxicity profile of ICIs, its relationship with the treatment response, and causes underlying the excellent treatment response in some patients, while recalcitrance in others. Research groups have continued to seek biomarkers that may permit the identification of treatment responders and predict toxicity to facilitate cessation of immunotherapy before the development of severe toxicity. However, some studies have found associations between serious adverse events and longer survivorship. The research question entailed determining whether a biomarker is needed to predict severe immune-related adverse events prior to their development or whether providing early treatment for toxicity would inhibit the immune system from attaining a long-lasting anti-tumor effect. Therefore, this review conducted an in-depth analysis into the molecular basis of these observations.

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Multimarker scores of Th1 and Th2 immune cellular profiles in peripheral blood predict response and immune related toxicity with CTLA4 blockade and IFNα in melanoma

Cited by 14 publications

References 51 publications

Systematic evaluation of the predictive gene expression signatures of immune checkpoint inhibitors in metastatic melanoma

Systematic evaluation of the predictive gene expression signatures of immune checkpoint inhibitors in metastatic melanoma

Immune Checkpoint Inhibitors in EGFR-Mutated NSCLC: Dusk or Dawn?

Predictive Biomarkers of Severe Immune-Related Adverse Events With Immune Checkpoint Inhibitors: Prevention, Underlying Causes, Intensity, and Consequences

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