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Immune status at pre-treatment impacts on progression-free survival of metastatic colorectal cancer patients treated with first-line chemotherapy
  1. Kohei Tada1,
  2. Shigehisa Kitano2,
  3. Hirokazu Shoji3,
  4. Takashi Nishimura4,
  5. Yasuhiro Shimada3,
  6. Kengo Nagashima5,
  7. Yoshitaka Honma3,
  8. Satoru Iwasa3,
  9. Natsuko Okita3,
  10. Atsuo Takashima3,
  11. Ken Kato3,
  12. Yasuhide Yamada3,
  13. Naoyuki Katayama6,
  14. Narikazu Boku3,
  15. Tetsuya Hamaguchi3 and
  16. Yuji Heike3
  1. Aff1 St. Lukes's International Hosp., Immunotherapy & Cell Therapy Tokyo Japan
  2. Aff2 grid.272242.30000000121685385Dept. of Exp. Therap., Natl. Cancer Ctr. Hosp. Tokyo Japan
  3. Aff3 grid.272242.30000000121685385National Cancer Center Hospital Tokyo Japan
  4. Aff4 Tokyo Jikei Medical University Tokyo Japan
  5. Aff5 grid.136304.30000000403701101Chiba University Chiba Japan
  6. Aff6 grid.260026.0000000040372555XMie University Graduate School of Medicine Tsu Japan

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Meeting abstracts


Immunological status in surgically resected specimens affects the outcome of ‘operable’ colorectal cancer patients. For example, a high number of tumor infiltrating lymphocytes, CD3+ cells, CD8+ cells, or CD45RO+ cells in a tumor is associated with improved prognosis. However, it has not been determined whether the immunological status in peripheral blood affects the outcome of ‘inoperable’ metastatic colorectal cancer (MCRC) patients. We investigated the impact of peripheral immunological status at pre-treatment on progression-free survival (PFS) of MCRC patients.


Peripheral blood was prospectively collected from consecutive MCRC patients (n=40) before they received a first-line chemotherapy. The quantity of each of 25 immune subsets, including monocytic myeloid-derived suppressor cells (M-MDSC, defined as Lineage-CD14+CD11b+CD33+HLA-DRlow/-) and effector memory T cells (TEM, defined as CD3+CD4+ or CD8+CD45RA-CCR7-) was measured using multicolor-flow cytometry. The patients were divided into high (> median) and low (< median) groups based on the median value for each immune subset. PFS was compared between the two patient groups.


Of the 25 immune subsets quantified, we identified a high quantity of M-MDSC, a low quantity of CD4+ TEM, or a low quantity of CD8+ TEM as adverse prognostic factors for PFS. Thus, patients with high M-MDSC, low CD4+ TEM or low CD8+ TEM had significantly shorter PFS than those with low M-MDSC, high CD4+ TEM, or high CD8+ TEM, respectively (p=0.004, 0.005, and 0.002, respectively). Ten (25%) patients had three adverse factors, 11 (27.5 %) patients had 2, 8 (20%) patients had one, and 11 (27.5%) patients had none. Patients were classified into two distinct prognostic groups based on the number of adverse factors that were present in each patient. The presence of 2 or 3 adverse factors (n=21, 52.5%) correlated with significantly shorter PFS compared to the presence of no or 1 adverse factor (n=19, 47.5%) (p=0.00001). In addition, multivariate analysis showed that the presence of 2 or 3 adverse factors was an independent poor prognostic factor for PFS (Hazard ratio, 10.2; 95% confidence interval, 2.9-35.9; p=0.0003) after adjustment for previously known prognostic factors.


These results suggest that peripheral immune status at pre-treatment impacts on the prognosis of MCRC patients treated with first-line chemotherapy.