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Colorectal Cancer Relapse Predicted by Immune Cell Infiltration

Dr. Schmit and colleagues found that immune cell infiltration of colorectal tumors can predict disease relapse in patients who undergo surgery with curative intent.

04/06/2021

A research team led by Stephanie Schmit, PhD, MPH, Genomic Medicine Institute, has found that immune cell infiltration of colorectal cancer (CRC) tumors can predict disease relapse in patients who undergo surgery with curative intent. Published in OncoImmunology, the findings may help lead to more targeted post-operative surveillance strategies, which ultimately would improve prognosis for CRC patients at high risk for relapse.

Although surgical resection remains the most effective curative treatment for patients with non-metastatic CRC, a significant number of patients relapse following surgery. Unfortunately, there are no reliable methods to predict which patients are at greatest risk or who might benefit most from adjuvant therapy (additional treatment given to improve the primary treatment’s effectiveness).

Increasing evidence suggests that CRC relapse is governed by the tumor microenvironment, or the variety of non-cancer cellular components of a tumor. Among those components are immune cells, such as lymphocytes (white blood cells), which are known to infiltrate tumors and have been implicated in disease prognosis.

“Moving beyond earlier studies that have primarily focused on lymphocytes, we examined tumor infiltration by a diverse range of immune cell subtypes using gene expression profiles of CRC tumors,” said Dr. Schmit. Dr. Schmit joined Cleveland Clinic from Moffitt Cancer Center in Tampa last August.

Innate and adaptive immune cell infiltration linked with relapse 

Harnessing data from 1,120 CRC patients across four independent datasets, the researchers estimated tumor immune infiltration by 22 immune cell types and then examined each type’s association with time to disease relapse, adjusting for other influences on prognosis, such as adjuvant therapy.

They found that both innate (nonspecific) and adaptive (acquired) immune cell types were associated with disease relapse. Specifically, a lower risk of disease relapse was associated with infiltration by CD4+ memory activated T cells, resting and activated NK cells, M1 macrophages, and activated dendritic cells. In contrast, a higher risk of disease relapse and more disease relapse events were associated with monocyte, M2 macrophage, neutrophil and resting mast cell infiltration.

Notably, CD4+ memory activated T cell infiltration was the strongest predictor of lower disease relapse risk even after accounting for known prognostic indicators, including adjuvant therapy.

“Our study underscores the use of tumor immune infiltration estimates as a biomarker for predicting disease relapse in CRC patients,” said Dr. Schmit. “Given the need for reliable predictors, our findings have translational potential to eventually guide the optimal clinical management of patients following surgery.”

Yasmin Kamal, PhD, an MD Candidate at Geisel School of Medicine at Dartmouth, is first author on this study, which was supported in part by the American Cancer Society, the Cancer Prevention Research Institute of Texas and the National Institutes of Health. Dr. Kamal trained as a graduate student with Dr. Schmit’s lab at Moffitt Cancer Center.



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