Immune overdrive signature in colorectal tumor subset predicts poor clinical outcome

Fakih, Marwan; Ouyang, Ching; Wang, Chongkai; Tu, Travis Y.; Gozo, Maricel; Cho, May; Sy, Marvin; Longmate, Jeffrey; Lee, Peter P.

doi:10.1172/jci127046

Cited by 68 publications

(70 citation statements)

References 60 publications

(65 reference statements)

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“…The immune cells in ltration levels in predicting the recurrence, metastasis, treatment response, and prognosis of CRC have been widely reported. 9,10,11,12,13,14,15 And immune-related prognostic model was constructed and validated in CRC too. 20 In order to explore whether the macrophage in ltration level play an important role in predicting the recurrence in stage CRC or not, we assessed the diagnostic e ciency of the macrophage in ltration level combined GRM (macrophage in ltration related-GRM) by ROC.…”

Section: Evaluation Of the Diagnostic E Ciency Of The Macrophage In Lmentioning

confidence: 99%

“…As macrophage in ltration level was negative correlated with recurrence in stage CRC, and recurrence is recognized as a poor prognostic factor. Given the immune cells in ltration levels are highly relevant to the progression and prognosis of CRC, 9,10,11,12,13,14,15,20 we aim to explore whether the macrophage in ltration level could predict the prognosis of stage CRC.…”

Section: Exploring the Clinical Values Of The Macrophage In Ltration mentioning

confidence: 99%

“…6,7,8 The immune cells in ltration levels highly related to the recurrence, metastasis, treatment response, and prognosis of CRC have been widely reported. 9,10,11,12,13,14,15 And the immune cell in ltration has shown superior prognostic power than the clinic pathological factors as TNM staging. 16 Recently, a large international validation effort demonstrated the reliable performance of the immune cell in ltration for estimating CRC patients' risk of recurrence.…”

Section: Introductionmentioning

confidence: 99%

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Tumor infiltrated macrophage-the fighter defends against recurrence of stage Ⅱcolorectal cancer

Yang

Wang

Zhang

et al. 2020

Preprint

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BackgroundBiomarkers which can robustly predict the recurrence of stage II colorectal cancer (CRC) have been urgent needed. Immune cells highly related to the recurrence and prognosis of CRC. However, whether the immune cells take part in the recurrence of stage II CRC has not known.MethodsExplored the roles and possible mechanism of immune cells in the recurrence of stage II CRC by public databases.ResultsTumor Immune Estimation Resource (TIMER) analysis indicated the macrophage infiltration level in stage II CRC: Significantly higher in the nonrecurrence group than that in the recurrence group; Significantly negative correlated with the recurrence-related hub gene transferrin (TF); Significantly positive correlated with the improved disease-free survival (DFS) and overall survival (OS). And macrophage infiltration related-gene recurrent model (GRM) (area under the curve (AUC) = 0.906) provide a better performance than the GRM established previously (AUC = 0.882) to predict the recurrence of stage II CRC. Gene Set Enrichment Analysis (GSEA) analysis indicated macrophage (M1) infiltrated in the tumor microenvironment (TME) defending against recurrence as a dynamic process: M1 was activated by receiving the stimulus signals (LPS/IFN- γ) which released by CRC cells, then infiltrating and recognizing the tumor to secrete IL-6 to directly or indirectly act on TF or create anti-tumor TME to kill tumor cells.ConclusionsThis study maybe provides a novel immunological perspective to explore the mechanism of recurrence and improve clinical practice performance in stage II CRC.

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Section: Evaluation Of the Diagnostic E Ciency Of The Macrophage In Lmentioning

confidence: 99%

Section: Exploring the Clinical Values Of The Macrophage In Ltration mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Tumor infiltrated macrophage-the fighter defends against recurrence of stage Ⅱcolorectal cancer

Yang

Wang

Zhang

et al. 2020

Preprint

View full text Add to dashboard Cite

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“…By 2030, its burden is expected to increase by 60%, and new cases were predicted to increase by 2.2 million, with 1.1 million cancer-related deaths [5]. Unfortunately, up-regulated PD-L1 expression can lead to poor prognosis in CRC patients [6], but the immune checkpoint inhibitors (ICIs) therapy has opened a new window, brining hope to patients with high PD-L1 expression. Current clinical studies revealed that patients with MSI/dMMR mCRC and MSI/dMMR non-CRC chemo-resistance metastasis demonstrated better e cacy with anti-PD-L1 therapy, with objective response rates of 40% and 57%, respectively [7].…”

Section: Introductionmentioning

confidence: 99%

Cerenkov luminescence imaging is an effective preclinical tool for assessing colorectal cancer PD-L1 levels in vivo

Zhao

Pan

Jiang

et al. 2020

Preprint

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Background: Preclinical and clinical studies have demonstrated that immunotherapy has effectively delayed tumor progression, and the clinical outcomes of anti-PD-1/PD-L1 therapy were related to PD-L1 expression level in the tumors. A 131I-labeled anti-PD-L1 monoclonal antibody tracer, 131I-PD-L1-Mab, was developed to study the target ability of non-invasive Cerenkov luminescence imaging in colorectal cancer xenograft mice.Method: Anti-PD-L1 monoclonal antibody labeled with 131I (131I-PD-L1-Mab), and in vitro binding assays were used to evaluate the affinity of 131I-PD-L1-Mab to PD-L1 and their binding level to different colorectal cancer cells, and compared with flow cytometry, western blot analysis, and immunofluorescence staining. The clinical application value of 131I-PD-L1-Mab was evaluated through biodistribution and Cerenkov luminescence imaging, and different tumor-bearing models expressing PD-L1 were evaluated.Results: 131I-PD-L1-Mab showed high affinity to PD-L1, and the equilibrium dissociation constant was 1.069×10-9M. The competitive inhibition assay further confirmed the specific binding ability of 131I-PD-L1-Mab. In four different tumor-bearing models with different PD-L1 expression, the biodistribution and Cerenkov luminescence imaging showed that the RKO tumors demonstrated the highest uptake of the tracer 131I-PD-L1-Mab, with a maximum uptake of 1.613 ± 0.738%IA/g at 48 h.Conclusions: There is a great potential for 131I-PD-L1-Mab noninvasive Cerenkov luminescence imaging to assess the status of tumor PD-L1 expression and select patients for anti-PD-L1 targeted therapy.

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“…By 2030, its burden is expected to increase by 60%, and new cases were predicted to increase by 2.2 million, with 1.1 million cancer-related deaths [5]. Unfortunately, up-regulated PD-L1 expression can lead to poor prognosis in CRC patients [6], but the immune checkpoint inhibitors (ICIs) therapy has opened a new window, brining hope to patients with high PD-L1 expression. Current clinical studies revealed that patients with MSI/dMMR mCRC and MSI/dMMR non-CRC chemo-resistance metastasis demonstrated better efficacy with anti-PD-L1 therapy, with objective response rates of 40% and 57%, respectively [7].…”

mentioning

confidence: 99%

Cerenkov luminescence imaging is an effective preclinical tool for assessing colorectal cancer PD-L1 levels in vivo

Zhao

Pan

Jiang

et al. 2020

Preprint

View full text Add to dashboard Cite

Background : Preclinical and clinical studies have demonstrated that immunotherapy has effectively delayed tumor progression, and the clinical outcomes of anti-PD-1/PD-L1 therapy were related to PD-L1 expression level in the tumors. A 131 I-labeled anti-PD-L1 monoclonal antibody tracer, 131 I-PD-L1-Mab, was developed to study the target ability of non-invasive Cerenkov luminescence imaging in colorectal cancer xenograft mice.Method: Anti-PD-L1 monoclonal antibody labeled with 131 I( 131 I-PD-L1-Mab), and in vitro binding assays were used to evaluate the affinity of 131 I-PD-L1-Mab to PD-L1 and their binding level to different colorectal cancer cells, and compared with flow cytometry, western blot analysis, and immunofluorescence staining. The clinical application value of 131 I-PD-L1-Mab was evaluated through biodistribution and Cerenkov luminescence imaging, and different tumor-bearing models expressing PD-L1 were evaluated.Results: 131 I-PD-L1-Mab showed high affinity to PD-L1, and the equilibrium dissociation constant was 1.069×10 -9 M. The competitive inhibition assay further confirmed the specific binding ability of 131 I-PD-L1-Mab. In four different tumor-bearing models with different PD-L1 expression, the biodistribution and Cerenkov luminescence imaging showed that the RKO tumors demonstrated the highest uptake of the tracer 131 I-PD-L1-Mab, with a maximum uptake of 1.613 ± 0.738% ID/g at 120 h.Conclusions: There is a great potential for 131 I-PD-L1-Mab noninvasive Cerenkov luminescence imaging to assess the status of tumor PD-L1 expression and select patients for anti-PD-L1 targeted therapy.

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Immune overdrive signature in colorectal tumor subset predicts poor clinical outcome

Cited by 68 publications

References 60 publications

Tumor infiltrated macrophage-the fighter defends against recurrence of stage Ⅱcolorectal cancer

Tumor infiltrated macrophage-the fighter defends against recurrence of stage Ⅱcolorectal cancer

Cerenkov luminescence imaging is an effective preclinical tool for assessing colorectal cancer PD-L1 levels in vivo

Cerenkov luminescence imaging is an effective preclinical tool for assessing colorectal cancer PD-L1 levels in vivo

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