Prognostic Utility of Immunoprofiling in Colon Cancer: Results from a Prospective, Multicenter Nodal Ultrastaging Trial

Flaherty, Devin C.; Lavotshkin, Simon; Jalas, John R.; Torisu‐Itakura, Hitoe; Kirchoff, Daniel D.; Sim, Myung Shin; Lee, Delphine J.; Bilchik, Anton J.

doi:10.1016/j.jamcollsurg.2016.03.003

Cited by 26 publications

(33 citation statements)

References 31 publications

(28 reference statements)

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“…Eighteen studies did not find any significant survival difference according to Tcell infiltration, although only 14 of these assessed independent cohorts [84,87,88,91,96,102,106,110,111,113,115,120,126,134]. Many studies compared more than one T-cell marker and included multiple inflammatory markers or MSI [70,81,83,92,95,132] in multivariate analysis [30,61,78,83,85,90,92,98,104,[117][118][119]127,130], with the result that although each marker was highly significant on univariate analysis, the survival advantage was not independent of other markers of inflammation. This suggests that a functional host immune response results in a better outcome, regardless of which markers are assessed.…”

Section: T-lymphocyte Subsetsmentioning

confidence: 99%

“…CD3, a generic T-cell marker expressed by the majority of T-cells [135], was assessed in thirty-four studies in relation to survival in rectal, colon or colorectal cancer, although two studies had overlapping cohorts [59,61]. There were, therefore, thirty-two independent cohorts comprising a total of 7947 patients [ found to have a significant positive association with survival in twentyfour of these, of which twenty-three were independent and comprised 5292 patients [30,58,60,63,[76][77][78][79][80][81]83,85,86,89,90,[92][93][94][95][97][98][99]127]. Ten studies found no significant association of CD3 with survival [59,68,82,84,87,88,91,96,102,118].…”

Section: Cd3 (Generic T-cell Marker)mentioning

confidence: 99%

“…In colon cancer, there were 6 studies comprising 591 patients that assessed the relation of CD3 infiltration with survival [58,61,[77][78][79]127]. All found a significant association with survival.…”

Section: Cd3 (Generic T-cell Marker)mentioning

confidence: 99%

“…Five of these (502 patients) assessed the intratumoural compartments [58,61,77,79,127]. Two assessed the invasive margin in addition to other areas of the slide [78,79]. Three studies compared different tumour regions in the same cohort and of these: one found that the IE CD3 was significant for survival, whereas ST CD3 was not [58]; one found both IM CD3 and total slide CD3 were significant for survival [78]; and one found that intratumoural CD3 was significant where IM CD3 was not [79].…”

Section: Cd3 (Generic T-cell Marker)mentioning

confidence: 99%

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The local inflammatory response in colorectal cancer – Type, location or density? A systematic review and meta-analysis

Alexander

McMillan

Park

2020

Cancer Treatment Reviews

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The host anti-tumour inflammatory response is a strong prognostic indicator, and tumour infiltrating lymphocytes (TILs) are believed to have a complimentary role alongside TNM assessment in dictating future management. However, there is wide disagreement regarding the most efficacious and cost-effective method of assessment. Methods: A comprehensive literature search was performed of EMBASE, MedLine and PubMed as well as an assessment of references to identify all relevant studies relating to the assessment of the peri-tumoural inflammatory response or TILs and prognosis in colorectal cancer (CRC). A meta-analysis was performed of 67 studies meeting the REMARK criteria using RevMan software. Results: Intratumoural assessment of both CD3 and CD8 in CRC were significant for disease-free survival (DFS) (combined HRs 0.46; 95%CI: 0.39-0.54 and 0.54; 95%CI: 0.45-0.65), as well as overall survival (OS) and disease-specific survival (DSS). The same was true for assessment of CD3 and CD8 at the invasive margin (DFS: combined HRs 0.45; 95%CI: 0.33-0.61 and 0.51; 95%CI: 0.41-0.62). However, similar fixed effects summaries were also observed for H&E-based methods, like Klintrup-Makinen grade (DFS: HR 0.62; 95%CI: 0.43-0.88). Furthermore, inflammatory assessments were independent of MSI status. Conclusion: The evidence suggests that it is the density of a coordinated local inflammatory infiltrate that confers survival benefit, rather than any individual immune cell subtype. Furthermore, the location of individual cells within the tumour microenvironment does not appear to influence survival. The authors advocate a standardised assessment of the local inflammatory response, but caution against emphasizing the importance of any individual immune cell subtype.

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Section: T-lymphocyte Subsetsmentioning

confidence: 99%

Section: Cd3 (Generic T-cell Marker)mentioning

confidence: 99%

Section: Cd3 (Generic T-cell Marker)mentioning

confidence: 99%

Section: Cd3 (Generic T-cell Marker)mentioning

confidence: 99%

See 2 more Smart Citations

The local inflammatory response in colorectal cancer – Type, location or density? A systematic review and meta-analysis

Alexander

McMillan

Park

2020

Cancer Treatment Reviews

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“…Therefore, including information that may enhance staging precision beyond the lymph node status is needed. Immunoprofiling has proven to be of prognostic relevance (14), and recently claimed to be superior to previous prognostic markers such as microsatellite instability (MSI) in CRC (15). However, there is a link between MSI and immune response in that previous studies have found that patients with MSI have a higher percentage of CD8 + T-cells, but a lower percentage of CD4 + T-cells in tumour compared to those with microsatellite stable (MSS) disease (16).…”

Section: Conclusion: There Is a Correlation Between Blood Cd3 + And Cmentioning

confidence: 99%

Correlation of Blood T-Cells to Intratumoural Density and Location of CD3+ and CD8+ T-Cells in Colorectal Cancer

Hagland

Lea

Watson

et al. 2017

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Nanomedicines as Multifunctional Modulators of Melanoma Immune Microenvironment

Carreira

Acúrcio

Matos

et al. 2020

Advanced Therapeutics

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Melanoma is the most destructive and deadly among skin cancers. Patients presenting the most disseminated form of this disease have very low survival rates (≈15%) and highly restricted therapeutic alternatives. In recent years, the area of cancer immunotherapy has witnessed remarkable developments in the management of many cancers, including melanoma. In fact, immunotherapy unveiled as a feasible therapeutic alternative for late‐stage melanoma patients, specifically using immune checkpoint therapies. However, despite the exciting outcomes, only a small percentage of patients respond to these therapies, and severe immune‐related adverse reactions have been often reported. As such, most of preclinical and clinical studies currently explore melanoma tumor biology and immunology to guide the development of combinational immunotherapies aiming at relevant clinical efficacy and minimal toxicity. Herein, the current knowledge on melanoma biology and immunology is discussed, focusing on nanotechnology as a crucial strategy for the development of combinatorial approaches able to specifically modulate the function of key players responsible for melanoma evolution and evasion of host immune‐mediated attacks. Finally, the major challenges toward the clinical implementation of these emergent targeted nanomedicines for immunotherapy are further discussed, with particular focus on melanoma genomics, predictive biomarkers, clinical trial design, and clinical regulation of nanomedicines.

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Prognostic Utility of Immunoprofiling in Colon Cancer: Results from a Prospective, Multicenter Nodal Ultrastaging Trial

Cited by 26 publications

References 31 publications

The local inflammatory response in colorectal cancer – Type, location or density? A systematic review and meta-analysis

The local inflammatory response in colorectal cancer – Type, location or density? A systematic review and meta-analysis

Correlation of Blood T-Cells to Intratumoural Density and Location of CD3+ and CD8+ T-Cells in Colorectal Cancer

Nanomedicines as Multifunctional Modulators of Melanoma Immune Microenvironment

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