Last Updated: December 22, 2005



NEW YORK (Reuters Health) - The presence in colorectal cancers of a
recently characterized immune cell population -- effector memory T
cells -- has a major impact on tumor evolution, according to European
investigators who have shown that these cells prevent colorectal
cancer dissemination and distant metastases and are associated with
prolonged survival.


Until now, the role of tumor-infiltrating immune cells in the early
metastatic invasion of colorectal cancer was largely unknown. "Our
data suggest that the tumor microenvironment and the host's immune
response are of major importance in tumor progression," the study
team concludes in their paper in the December 22nd issue of The New
England Journal of Medicine.

In their analysis of 959 resected colorectal tumor specimens, early
conventional pathological tumor-node-metastasis stage and the absence
of early metastatic invasion -- venous emboli, lymphatic invasion,
and perineural invasion, collectively termed VELIPI -- were
independently associated with increased survival.

Moreover, according to Dr. Jerome Galon, a research scientist at
INSERM, the French National Institute of Health and Medical Research
in Paris, "a high-density of intratumoral effector memory T cells
significantly correlated with VELIPI-negative tumors. In contrast, a
low-density of intratumoral effector-memory T cells significantly
correlated with tumor dissemination (VELIPI-positive), lymph-node
metastasis, distant metastasis, and shorter survival."

It may be possible, Dr. Galon said, to classify tumors based on the
density of these immune cells "with better predictive value than the
gold-standard histo-prognostic classification, which is based on
tumor criteria only. This will allow us to define patient groups with
high-risk of relapse justifying adjuvant therapy."

In addition, the amplification or stimulation of these effector
memory cells could be used as a novel immunotherapy for the treatment
of colorectal cancer and possibly other cancers as well, Dr. Galon
noted.

Dr. Giorgio Parmiani from the National Tumor Institute in Milan notes
in an editorial that these data provide "strong but indirect evidence
of immune-mediated control of the growth of colorectal cancer."

"What we lack are functional studies showing an ongoing, tumor-
specific immune response mediated by T cells in untreated patients
with colorectal cancer," the researcher notes.

Nonetheless, there is "convincing evidence," Dr. Parmiani notes, of
an association between a favorable prognosis and the infiltration by
cytotoxic cytokine-releasing effector memory CD8+ T cells into
melanoma, ovarian cancer, non-Hodgkin's lymphoma, and now colorectal
cancer.