Longitudinal Assessment of Tumor-Infiltrating Lymphocytes in Primary Breast Cancer Following Neoadjuvant Radiation Therapy.
ICR Authors
Authors
Yoneyama, M
Zormpas-Petridis, K
Robinson, R
Sobhani, F
Provenzano, E
Steel, H
Lightowlers, S
Towns, C
Castillo, SP
Anbalagan, S
Lund, T
Wennerberg, E
Melcher, A
Coles, CE
Roxanis, I
Yuan, Y
Somaiah, N
Zormpas-Petridis, K
Robinson, R
Sobhani, F
Provenzano, E
Steel, H
Lightowlers, S
Towns, C
Castillo, SP
Anbalagan, S
Lund, T
Wennerberg, E
Melcher, A
Coles, CE
Roxanis, I
Yuan, Y
Somaiah, N
Document Type
Journal Article
Date
2024-11-01
Date Accepted
2024-04-21
Date Available
2024-07-08T10:04:36Z
Abstract
PURPOSE: Tumor-infiltrating lymphocytes (TILs) have prognostic significance in several cancers, including breast cancer. Despite interest in combining radiation therapy with immunotherapy, little is known about the effect of radiation therapy itself on the tumor-immune microenvironment, including TILs. Here, we interrogated longitudinal dynamics of TILs and systemic lymphocytes in patient samples taken before, during, and after neoadjuvant radiation therapy (NART) from PRADA and Neo-RT breast clinical trials. METHODS AND MATERIALS: We manually scored stromal TILs (sTILs) from longitudinal tumor samples using standardized guidelines as well as deep learning-based scores at cell-level (cTIL) and cell- and tissue-level combination analyses (SuperTIL). In parallel, we interrogated absolute lymphocyte counts from routine blood tests at corresponding time points during treatment. Exploratory analyses studied the relationship between TILs and pathologic complete response (pCR) and long-term outcomes. RESULTS: Patients receiving NART experienced a significant and uniform decrease in sTILs that did not recover at the time of surgery (P < .0001). This lymphodepletive effect was also mirrored in peripheral blood. Our SuperTIL deep learning score showed good concordance with manual sTILs and importantly performed comparably to manual scores in predicting pCR from diagnostic biopsies. The analysis suggested an association between baseline sTILs and pCR, as well as sTILs at surgery and relapse, in patients receiving NART. CONCLUSIONS: This study provides novel insights into TIL dynamics in the context of NART in breast cancer and demonstrates the potential for artificial intelligence to assist routine pathology. We have identified trends that warrant further interrogation and have a bearing on future radioimmunotherapy trials.
Citation
International Journal of Radiation Oncology Biology Physics, 2024, pp. S0360-3016(24)00566-2 -
Source Title
International Journal of Radiation Oncology Biology Physics
Publisher
ELSEVIER SCIENCE INC
ISSN
0360-3016
eISSN
1879-355X
1879-355X
1879-355X
Collections
Research Team
Trans Breast Radiobiol