Factors affecting tumor responders and predictive biomarkers of toxicities in cancer patients treated with immune checkpoint inhibitors

Yao, Liqin; Jia, Gang; Lu, Lingeng; Bao, Ying; Ma, Wenxue

doi:10.1016/j.intimp.2020.106628

Cited by 21 publications

(13 citation statements)

References 138 publications

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“…We investigated the correlations between ctDNA and irAEs, and found that patients with alterations in CEBPA (100% vs 27.3%, p = 0.09), FGFR4(100% vs 27.3%, p = 0.09), MET (100% vs 27.3%, p = 0.09), or KMT2B(100% vs 27.3%, p = 0.09) in baseline plasma had greater likelihood of experiencing irAEs, which requires further independent validation in a clinical trial setting with more patients enrolled. Previous studies showed that plentiful biomarkers, including gender, serum cytokines, immune cells, and autoantibodies, were associated with the occurrence of high-grade irAEs [ 10 ]. However, there is not any biomarker with high grade of evidence level, more predictive biomarkers of irAEs deserved to be investigated.…”

Section: Resultsmentioning

confidence: 99%

The predicting role of circulating tumor DNA landscape in gastric cancer patients treated with immune checkpoint inhibitors

et al. 2020

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A more common and noninvasive predicting biomarker for programmed cell death 1 (PD-1) antibody remains to be explored. We assessed 46 patients with advanced gastric cancer who received PD-1 antibody immunotherapy and 425-genes next-generation sequencing (NGS) testing. Patients who had a > 25% decline in maximal somatic variant allelic frequency (maxVAF) had a longer progression free survival (PFS) and higher response rate than those who did not (7.3 months vs 3.6 months, p = 0.0011; 53.3% vs 13.3%, p = 0.06). The median PFS of patients with undetectable and detectable post-treatment circulating tumor DNA (ctDNA) was 7.4 months vs. 4.9 months (p = 0.025). Mutation status of TGFBR2, RHOA, and PREX2 in baseline ctDNA influenced the PFS of immunotherapy (p < 0.05). Patients with alterations in CEBPA, FGFR4, MET or KMT2B (p = 0.09) gene had greater likelihood of immune-related adverse events (irAEs). ctDNA can serve as a potential biomarker of the response to immunotherapy in advanced gastric cancers, and its potential role in predicting irAEs worth further exploration.

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Section: Resultsmentioning

confidence: 99%

The predicting role of circulating tumor DNA landscape in gastric cancer patients treated with immune checkpoint inhibitors

et al. 2020

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“…Immunotherapy has brought a huge revolution to the treatment of cancer. Recent developments in immune checkpoint blockade therapy (ICB) have resulted in increased success for patients with CD274 (also known as PDL1), PDCD1 (also known as PD1), and CTLA4 [ 20 ]. Mehnert et al [ 21 ] found through a clinical trial on PTC (NCT02054806) that pembrolizumab (PD-1 inhibitor) not only exerts anti-tumor activity, but also has controllable safety.…”

Section: Introductionmentioning

confidence: 99%

Evaluate the diagnostic and prognostic value of NUSAP1 in papillary thyroid carcinoma and identify the relationship with genes, proteins, and immune factors

et al. 2022

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Background Nucleolar spindle-associated protein 1 (NUSAP1) is reported to be a useful diagnostic and prognostic marker for a variety of cancers, but relevant studies are lacking in papillary thyroid carcinoma (PTC). Methods The relationship between NUSAP1 expression and the overall survival (OS) of pan-cancer was examined by GEPIA and KMplot. We explored the relationship between NUSAP1 and clinical PTC data based on the THCA dataset of TCGA and the GEO dataset of NCBI; GO, KEGG analysis, and ceRNA networks were performed on co-expressed genes through LinkedOmics and Starbase. We assessed the relevance between NUSAP1 and the tumor microenvironment using ESTIMATE, correlations between NUSAP1 and immune cells with TIMER, the relationship between NUSAP1 and immunotherapy by TCIA, and small-molecule drugs targeting NUSAP1 that can be discovered using the CMap database. Results Higher expression of NUSAP1 in pan-cancer tissues was correlated with shorter OS. NUSAP1 was also significantly expressed in PTC tissues and was an independent prognostic risk factor. Compared to the NUSAP1 low expression group, the NUSAP1 high expression group was more likely to also have lymph node metastasis, pathological PTC type, shorter progression-free survival (PFS), and higher scores for immune checkpoint inhibitor treatment. The genes associated with NUSAP1 were mostly involved in the cell cycle, immune-related pathways, and AITD. Ten lncRNAs (GAS5, SNHG7, UCA1, SNHG1, HCP5, DLEU2, HOTAIR, TP53TG1, SNHG12, C9orf106), eleven miRNAs (hsa-miR-10a-5p, hsa-miR-10b-5p, hsa-miR-18a-5p, hsa-miR-18b-5p, hsa-miR-128-3p, hsa-miR-214-3p, hsa-miR-219a-2-3p, hsa-miR-339-5p, hsa-miR-494-3p, hsa-miR-545-3p, hsa-miR-769-5p), and one mRNA (NUSAP1) were constructed. NUSAP1 participated in the formation of the tumor microenvironment. CMap predicted the 10 most important small molecules about NUSAP1. Conclusions In PTC, NUSAP1 shows good diagnostic value and prognostic value; NUSAP1 impacts the cell cycle, immune-related pathways, and AITD and has a complex effect on the tumor microenvironment in PTC.

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“…There is no evidence that immune-related endocrine adverse events affect the prognosis of patients with advanced lung cancer. Immune-related adverse events (IrAEs) can occur during the course of immunotherapy ( 24 ), so follow-up monitoring is also important. Thyroid autoantibody tests and radioactive iodine uptake rate should be performed prior to the use of PD-1 inhibitors, and thyroid-related indicators should be monitored after treatment, especially in the first 1 to 2 months of treatment, to determine the cause of thyroid dysfunction, so that appropriate treatment can be given to improve the prognosis of patients.…”

Section: Discussionmentioning

confidence: 99%

Immunochemotherapy includes pembrolizumab for stage IIIB lung squamous cell carcinoma: a case report

Zhang¹,

Huang²,

Chen³

et al. 2022

Ann Transl Med

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Background: Lung cancer is a malignant tumor with high morbidity and mortality, and its incidence continues to increase. With the emergence of new drugs and treatment modalities, the prognosis of lung cancer patients has improved to some extent. However, the prognosis of initially unresectable, locally advanced lung cancer with immunotherapy combined with chemotherapy remains uncertain.Case Description: We report a case of a 57-year-old man diagnosed with stage IIIB la with negative targeted therapy-related gene mutation and a 2% programmed death 1/programmed cell death-ligand 1 (PD-1/PD-L1) expression level, who underwent transformation treatment with pembrolizumab after multidisciplinary consultation. Lung images indicated partial response after 4 cycles. However, preoperative examination found hypothyroidism considered the immune-related, and giving hormone replacement treatment after the endocrinology department consultation. Thyroid function improved after 1 month.The patient successfully underwent single-hole thoracoscopic radical lung cancer (left whole lung resection + mediastinal lymph node dissection). Postoperative pathology was consistent with major pathological remission (MPR). The patient was scheduled to receive 8 cycles of single-drug maintenance therapy with pembrolizumab after surgery. To date, no tumor recurrence and metastasis have been found at follow up, and maintenance treatment continues to improve.Conclusions: This case reminds us that the induction treatment pattern of pembrolizumab combined with chemotherapy for subsequent conversion surgery can be a potentially curative treatment option for locally advanced stage IIIB patients. The monitoring of thyroid-related indicators is important during immunotherapy, especially in the first 1-2 months. The cause of thyroid dysfunction should be detected early so that it can be treated promptly to improve the prognosis of the patient. Pembrolizumab in combination with paclitaxel and platinum drugs provides a new option for patients with locally advanced stage IIIB lung squamous cell carcinoma who eager to undergo radical surgery.

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Factors affecting tumor responders and predictive biomarkers of toxicities in cancer patients treated with immune checkpoint inhibitors

Cited by 21 publications

References 138 publications

The predicting role of circulating tumor DNA landscape in gastric cancer patients treated with immune checkpoint inhibitors

The predicting role of circulating tumor DNA landscape in gastric cancer patients treated with immune checkpoint inhibitors

Evaluate the diagnostic and prognostic value of NUSAP1 in papillary thyroid carcinoma and identify the relationship with genes, proteins, and immune factors

Immunochemotherapy includes pembrolizumab for stage IIIB lung squamous cell carcinoma: a case report

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