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. 2025 Jul 31;17(7):4409-4419.
doi: 10.21037/jtd-2025-526. Epub 2025 Jul 28.

Predictive role of tumor-infiltrating lymphocytes and immune phenotype for pembrolizumab in relapsed or refractory thymic carcinoma

Dong Hyun Kim  1   2 , Yoojoo Lim  3 , Sanghoon Song  3 , Chan-Young Ock  3 , Jeonghwan Youk  1   4 , Miso Kim  1   4 , Tae Min Kim  1   4 , Dong-Wan Kim  1   4 , Hak Jae Kim  5 , Jiwon Koh  4   6 , Kyeong Cheon Jung  6 , Kwon Joong Na  7 , Chang Hyun Kang  7 , Bhumsuk Keam  1   4
Affiliations

Predictive role of tumor-infiltrating lymphocytes and immune phenotype for pembrolizumab in relapsed or refractory thymic carcinoma

Dong Hyun Kim et al. J Thorac Dis. .

Abstract

Background: Pembrolizumab is a promising treatment option for platinum-failed thymic carcinoma; however, the lack of established predictive biomarkers remains a challenge. Therefore, this study aimed to assess the predictive value of artificial intelligence (AI)-powered tumor-infiltrating lymphocyte (TIL) analysis of pembrolizumab for thymic carcinoma.

Methods: Patients with platinum-failed, advanced thymic carcinoma treated with pembrolizumab between January 2016 and December 2021 were included. Hematoxylin and eosin-stained sections from the samples closest to the time before pembrolizumab treatment were analyzed using an AI-powered TIL analyzer. Intratumoral TIL (iTILs) and stromal TIL (sTILs) were quantified, and their immune phenotypes (IP) were identified.

Results: In total, 10 patients were included in this study. The best response was complete response in 1 patient (10%) and partial response in 1 patient (10%). The median progression-free survival (PFS) was 5.0 months. Patients with higher iTIL (>27.23/mm2) exhibited longer PFS (median, 9.5 vs. 1.5 months, P=0.03) and overall survival (OS) (median, not determined vs. 4 months, P=0.03). Patients with higher sTIL (>252.54/mm2) exhibited longer PFS (median, 10 vs. 1 month, P=0.006) and OS (median, not determined vs. 9 months, P=0.01). Patients with inflamed IP exhibited longer PFS than those with non-inflamed IP (median, 10 vs. 3 months, P=0.046).

Conclusions: Increased infiltration of both iTIL and sTIL is associated with longer PFS and OS. Additionally, an inflamed IP is associated with longer PFS. Thus, TIL density and IP may be promising predictive biomarkers for pembrolizumab in patients with platinum-failed thymic carcinoma.

Keywords: Thymic carcinoma; artificial intelligence (AI); immune phenotype; pembrolizumab; tumor-infiltrating lymphocyte (TIL).

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-526/coif). Y.L. and S.S. are from Lunit Inc., Seoul, Republic of Korea. C.Y.O. holds a leadership position at Lunit and owns stocks in the company. D.W.K. receives research funding from Alpha Biopharma, Amgen, Astrazeneca/Medimmune, Boehringer-Ingelheim, Bridge BioTherapeutics, Chong Keun Dang, Daiichi-Sankyo, GSK, Hanmi, InnoN, IQVIA, Janssen, Merck, Merus, Mirati Therapeutics, MSD, Novartis, ONO Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Xcovery, Yuhan. K.J.N. is a cofounder and chief medical officer of Portrai, Inc. B.K. receives research funding from MSD, AstraZeneca, and Ono Pharmaceutical Co., Ltd., and has served as an advisor for Handok, NeoImmuneTec, Trialinformatics and ImmuneOncia outside of the current work. The other authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Details of cohort assembly strategy. IP, immune phenotype; TIL, tumor-infiltrating lymphocyte; R/R, relapsed or refractory.
Figure 2
Figure 2
Representative image of Lunit SCOPE IO. Representative image of H&E original image (A) and Lunit SCOPE IO-inferred segmentation of cancer epithelium (orange), cancer stroma (grass green), and TIL (cyan blue) (B). H&E, hematoxylin and eosinTIL, tumor-infiltrating lymphocyte.
Figure 3
Figure 3
Survival outcomes based on TIL density. (A) Kaplan-Meier curves of OS based on intratumoral TIL density. (B) Kaplan-Meier curves of PFS based on intratumoral TIL density. (C) Kaplan-Meier curves of OS based on stromal TIL density. (D) Kaplan-Meier curves of PFS based on stromal TIL density. OS, overall survival; PFS, progression-free survival; TIL, tumor-infiltrating lymphocyte.
Figure 4
Figure 4
Survival outcomes based on IP. (A) Kaplan-Meier curves of progression-free survival based on IP. (B) Kaplan-Meier curves of overall survival based on IP. IP, immune phenotype.
See this image and copyright information in PMC

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