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Colon Cancer Metastases are not Infiltrated by Favorably Prognostic T Cells: Evidence for the Escape Phase of the Cancer Immunoediting Hypothesis in Humans
*Bryan P Stanifer, *Arief Suriawinata, *Jiang Gui, Richard J Barth, Jr
Dartmouth-Hitchcock Medical Center, Lebanon, NH

Objective: The cancer immunoediting theory postulates three states of interaction between the immune system and cancer: elimination, equilibrium and escape. Evidence that the T cell immune response at the site of primary colorectal cancers is a strong predictor of survival supports the concept that primary tumors are in a state of equilibrium. We sought to determine if colorectal cancer metastases were in the escape phase of interaction by evaluating cytotoxic, memory and regulatory T cell immune responses at the site of colorectal cancer metastases and determining whether these responses are associated with patient survival.
Design: Pathologic analysis of specimens from a prospectively maintained clinical database.
Setting: Academic cancer center.
Patients: Eighty nine patients with resected hepatic colorectal metastases.
Intervention: None.
Outcome measures: We quantitated the number of CD8, CD45RO, and Fox P3 positive cells at the site of hepatic colorectal metastases by immunohistochemistry. The CD8 and CD45RO responses were used to calculate a total immune score. Previously established clinical recurrence scores were calculated.
Results: Four clinical recurrence scores all predicted patient survival. The T cell response, in cells per 5 high powered fields, at the site of the metastases was significantly greater than responses in normal liver: CD8: 57 vs 10, CD45RO: 90 vs 11, and Fox P3: 7 vs 0.4 (all p < 0.001). However, there was no association between patient survival and CD8, CD45RO, Fox P3 or the total immune score.
Conclusions: Unlike primary colorectal cancer, more robust T cell infiltration at the site of metastatic colorectal cancer is not associated with improved survival. This supports the immunoediting theory that cancer metastases exist in a state that has escaped from immune control.


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