Tumor-specific immune response after systemic anti-tumor therapy in patients with primary and metastatic breast cancer and its prediction for systemic relapse

Breast cancer is an immunological tumor that can induce a tumor antigen-specific immune response by developing tumor antigen-reactive CD45R0 Memory T-cells (trMTC) as detectable in bone marrow by INF-γ EliSpot analysis. Less is known, however, about the effect of systemic therapies on specific immune cells.

We compared bone marrow trMTC levels at the time of the first surgical procedure with immune responses after 1 year in 18 primary breast cancer patients without any signs of tumor recurrence. Furthermore, we analysed 36 patients after neoadjuvant chemotherapy and compared their immune status with that of untreated patients. Finally, we measured trMTC in 69 metastatic breast cancer patients who had heavily been pretreated chemotherapeutically.

After neoadjuvant chemotherapy patients' immune responses were significantly less positive and – if present – frequency of tumor antigen-reactive CD45R0 MTC was significantly lower in comparison to untreated patients (30% vs. 42% trMTC-positivity, p=0,03). In metastatic patients we were able to find lower immune response rates and trMTC frequencies as well (23%). In patients adjuvantly treated with hormonal therapy we did not see any significant immunological changes. In the adjuvant chemotherapy group, the presence of trMTC turned from positive to negative in 3 patients and from negative to positive in another 3 patients one year after primary surgery. 75% of patients pretreated with adjuvant chemotherapy and being trMTC positive one year after initial surgery showed distant metastasis in a long-term follow-up.

Thus, chemotherapies seem to have a great influence on the presence as well as the frequency of trMTC. Presence of trMTC in the follow-up period might be an indicator of persisting tumor disease and distant metastasis.