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Updated: Oct 4, 2025
Evaluation of Tumor-infiltrating Leukocyte Subsets in a Subcutaneous Tumor Model
Published on: April 13, 2015
Tumor-Infiltrating Lymphocyte Function Predicts Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal
Joseph Cherng Huei Kong1, Glen Robert Guerra1, Rosemary Magdalena Millen1
1Joseph Cherng Huei Kong, Glen Robert Guerra, Rosemary Magdalena Millen, Sara Roth, Huiling Xu, Paul Joseph Neeson, Phillip Kevin Darcy, Michael Henry Kershaw, Shienny Sampurno, Jordane Malaterre, David Shi Hao Liu, Toan Duc Pham, Vignesh Narasimhan, Minyu Wang, Yu-Kuan Huang, Jacob McCormick, Andrew Craig Lynch, Satish Warrier, Michael Michael, Jayesh Desai, William Murray, Catherine Mitchell, Samuel Ngan, Wayne Allen Phillips, Alexander Graham Heriot, and Robert George Ramsay, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne; and Kumar Visvanathan and Rosemary Magdalena Millen, St Vincent's Hospital, East Melbourne, Australia.
A new assay measures tumor-infiltrating lymphocyte (TIL) function in rectal cancer patients, predicting pathologic complete response (pCR). This functional assessment can guide treatment and aid in developing checkpoint inhibition blockade (CIB) therapies.
Area of Science:
- Oncology
- Immunology
- Cancer Research
Background:
- Tumor-infiltrating lymphocytes (TILs) predict outcomes, but their function is key.
- Conventional staging doesn't capture TIL functionality.
- Assessing TIL function is crucial for personalized rectal cancer treatment.
Purpose of the Study:
- Develop an assay to test TIL cytotoxicity in locally advanced rectal cancer patients before treatment.
- Identify patients likely to achieve a pathologic complete response (pCR).
- Demonstrate TIL function rescue after checkpoint inhibition blockade (CIB).
Main Methods:
- An in vitro cytotoxic assay using rectal cancer tumoroids and patient-matched TILs was established.
- TIL-mediated tumoroid lysis was measured via propidium iodide fluorescence.
- Checkpoint inhibition blockade (anti-PD-1) response was assessed.
Main Results:
- The assay identified patients achieving pCR with significantly higher TIL cytotoxicity (mean fluorescence intensity 27,982 vs. 12,428; p < .001).
- Checkpoint inhibition blockade partially restored TIL cytotoxicity in specimens with PD-1 expression.
Conclusions:
- TIL function evaluation is feasible within weeks of biopsy, potentially altering patient management.
- The assay can refine selection for watch-and-wait protocols.
- This cytotoxic assay platform can support further CIB development.
