Clinical Outcomes Associated with T Cell Changes Following Chemotherapy - Expert Commentary

Chemotherapy can alter the antitumor immune response, which is a critical target of immune checkpoint inhibitor treatment, van Wilpe et al. aimed to characterize changes in lymphocytes in patients treated with cisplatin-based chemotherapy.

The study consisted of 81 muscle-invasive bladder cancer patients who had upfront radical cystectomy or received at least two cycles of cisplatin-based chemotherapy before undergoing radical cystectomy. The number of intratumoral CD3+ and CD3+/CD8-/FoxP3- cells decreased slightly after neoadjuvant chemotherapy relative to baseline, while this change was not detected in the other immune cells subgroups. To correlate lymphocyte density with clinical outcomes, van Wilpe et al. divided patients into patients who exhibited recurrence within one year after cystectomy and patients who did not. Patients who were disease-free at one year showed stable or slightly increased intratumoral lymphocyte density, while patients who developed recurrence exhibited a decrease in intratumoral CD3+, CD3+/CD8-/FoxP3-, and CD3+/FoxP3+ after chemotherapy. In a univariate cox proportional hazards analysis, the change in CD3+ and CD3+/CD8-/FoxP3- density in patients treated with neoadjuvant chemotherapy was significantly related to the time to disease recurrence. The investigators also investigated lymphocyte density in the cystectomy tissue of a subset of patients who had a complete response to treatment or downstaging. Since there was no residual tumor tissue in these patients, researchers examined immune cell infiltration in tissues that were deemed likely to have contained cancer cells. Lymphocyte density was significantly decreased in these regions compared to the tumor surrounding regions in TURBT samples.

The findings from this study reveal that tumor-infiltrating lymphocyte density is a potential prognostic marker in patients undergoing neoadjuvant chemotherapy. One limitation of this study is the absence of various timepoints during chemotherapy treatment. This is important as a previous study indicated that lymphocyte density increases initially but decreases by the end of chemotherapy. Finally, additional studies are required to evaluate immune responses in patients undergoing a combination of neoadjuvant chemotherapy and immune checkpoint inhibitor therapy.

Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York

References:

  1. van Wilpe S, Sultan S, Gorris MAJ, et al. Intratumoral T cell depletion following neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer is associated with poor clinical outcome [published online ahead of print, 2022 Jun 30]. Cancer Immunol Immunother. 2022;10.1007/s00262-022-03234-0. doi:10.1007/s00262-022-03234-0

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