TY - JOUR
T1 - Tumor-Infiltrating Lymphocytes (TILs) as a Biomarker of Abscopal Effect of Cryoablation in Breast Cancer
T2 - A Pilot Study
AU - Khan, Sonia Y.
AU - Melkus, Michael W.
AU - Rasha, Fahmida
AU - Castro, Maribel
AU - Chu, Victoria
AU - Brandi, Luis
AU - Khan, Hafiz
AU - Gill, Harvinder Singh
AU - Pruitt, Kevin
AU - Layeequr Rahman, Rakhshanda
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/5
Y1 - 2022/5
N2 - Background: Morphological evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer is gaining momentum as an immunological biomarker. This experiment evaluates the role of TILs in distant tumors as a measure of abscopal effect from cryoablation of breast cancer. Methods: BALB/c mice underwent bilateral orthotopic transplant with 4T1-12B (triple-negative) cells. At 2 weeks, left tumors were treated by either resection (standard of care group) or cryoablation (intervention group) followed by resection of the distant right tumors 1 week posttreatment. TIL scores were calculated from hematoxylin and eosin-stained sections and phenotyped for cytotoxic T-lymphocyte (CTL) markers by immunofluorescence. Primarily resected tumors served as baseline (Tbaseline), whereas resected distant right-sided served as the readout for abscopal effect (AbsRes or AbsCryo). Mice were monitored for tumor recurrence and metastasis. Results: The AbsCryo had a significant mean (SD) increase in stromal (2.8 [1.1]%; p = 0.015) and invasive margin TILs (50 [12]%; p = 0.02) compared with TBaseline (1.0 [0]% and 31 [4.9]%, respectively). CTL phenotyping revealed a significant increase in mean (SD) CD8+ T cells (15.7 [12.1]; p = 0.02) and granzyme B (4.8 [3.6]; p = 0.048) for the AbsCryo compared with TBaseline (5.2 [4.7] and 2.4 [0.9], respectively). Posttreatment, the cryoablation group had no recurrence or metastasis, whereas the resected group showed local recurrence and lung metastasis in 40% of the mice. Postprocedure increase in TIL score of distant tumors was associated with decrease in tumor relapse (p = 0.02). Conclusions: Cryoablation induced a robust tumor-specific TIL response compared with resection, suggesting an abscopal effect leading to the prevention of cancer recurrence and metastasis.
AB - Background: Morphological evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer is gaining momentum as an immunological biomarker. This experiment evaluates the role of TILs in distant tumors as a measure of abscopal effect from cryoablation of breast cancer. Methods: BALB/c mice underwent bilateral orthotopic transplant with 4T1-12B (triple-negative) cells. At 2 weeks, left tumors were treated by either resection (standard of care group) or cryoablation (intervention group) followed by resection of the distant right tumors 1 week posttreatment. TIL scores were calculated from hematoxylin and eosin-stained sections and phenotyped for cytotoxic T-lymphocyte (CTL) markers by immunofluorescence. Primarily resected tumors served as baseline (Tbaseline), whereas resected distant right-sided served as the readout for abscopal effect (AbsRes or AbsCryo). Mice were monitored for tumor recurrence and metastasis. Results: The AbsCryo had a significant mean (SD) increase in stromal (2.8 [1.1]%; p = 0.015) and invasive margin TILs (50 [12]%; p = 0.02) compared with TBaseline (1.0 [0]% and 31 [4.9]%, respectively). CTL phenotyping revealed a significant increase in mean (SD) CD8+ T cells (15.7 [12.1]; p = 0.02) and granzyme B (4.8 [3.6]; p = 0.048) for the AbsCryo compared with TBaseline (5.2 [4.7] and 2.4 [0.9], respectively). Posttreatment, the cryoablation group had no recurrence or metastasis, whereas the resected group showed local recurrence and lung metastasis in 40% of the mice. Postprocedure increase in TIL score of distant tumors was associated with decrease in tumor relapse (p = 0.02). Conclusions: Cryoablation induced a robust tumor-specific TIL response compared with resection, suggesting an abscopal effect leading to the prevention of cancer recurrence and metastasis.
UR - http://www.scopus.com/inward/record.url?scp=85123837938&partnerID=8YFLogxK
U2 - 10.1245/s10434-021-11157-w
DO - 10.1245/s10434-021-11157-w
M3 - Article
C2 - 35094188
AN - SCOPUS:85123837938
SN - 1068-9265
VL - 29
SP - 2914
EP - 2925
JO - Annals of Surgical Oncology
JF - Annals of Surgical Oncology
IS - 5
ER -