bims-tuinly 2025-01-26 papers

Front Immunol. 2024 ;15 1511866

The global trends and distribution in tumor-infiltrating lymphocytes over the past 49 years: bibliometric and visualized analysis.

Beibei Wu, Ding Luo, Xuejie Wang, Chen Qiao, Rui Li, Jian Liu.

Background: The body of research on tumor-infiltrating lymphocytes (TILs) is expanding rapidly; yet, a comprehensive analysis of related publications has been notably absent.
Objective: This study utilizes bibliometric methodologies to identify emerging research hotspots and to map the distribution of tumor-infiltrating lymphocyte research.
Methods: Literature from the Web of Science database was analyzed and visualized using VOSviewer, CiteSpace, Scimago Graphica, R-bibliometrix, and R packages.
Results: Research on tumor-infiltrating lymphocytes began in 1975 and has experienced significant growth, particularly after 2015. Leading contributors include the United States, the National Cancer Institute, the journal Cancer Immunology Immunotherapy, and researcher Steven A. Rosenberg. Other prominent contributors include China, the National Institutes of Health, researcher Roberto Salgado, and the Journal of Immunology. Prominent institutions in the USA and Europe occupy central roles within collaborative networks. Financial support plays a pivotal role in driving research advancements. Keyword clustering analysis reveals four primary knowledge domains: adoptive cell therapy; the prognostic value of TILs; PD-1/PD-L1 and TILs; and prognostic studies of TILs across various cancers. Keyword and reference analyses further indicate that "adoptive cell therapy," "the prognostic value of TILs," and "immune checkpoint inhibitors and TILs" are central themes in current and future research. Combination therapies; tumor neoantigens; gene editing; dominant population selection of TILs therapy; TILs in Tumor microenvironment; emerging predictive biomarkers; TILs in predicting the efficacy of neoadjuvant chemotherapy and immunotherapy; the relationship between TILs and PD-L1; TIL-based patient stratification; tertiary lymphoid structures; and TIL evaluation through digital pathology and artificial intelligence are identified as key areas of interest.
Conclusions: This analysis highlights the increasing academic focus on tumor-infiltrating lymphocyte research and identifies key recent themes in the field such as prognostic value of TILs, personalized treatments, and combination therapies.

Keywords: PD-L1; adoptive cell therapy; bibliometrics; predictive biomarker; tumor-infiltrating lymphocytes

DOI: https://doi.org/10.3389/fimmu.2024.1511866

J Immunother Cancer. 2025 Jan 20. pii: e010207. [Epub ahead of print]13(1):

Art of TIL immunotherapy: SITC's perspective on demystifying a complex treatment.

Simon Turcotte, Marco Donia, Brian Gastman, Michal Besser, Robert Brown, George Coukos, Benjamin Creelan, John Mullinax, Vernon K Sondak, James C Yang, Maartje W Rohaan, Inge Marie Svane, Michael T Lotze, John B A G Haanen, Stephanie L Goff.

In a first for solid cancers, cellular immunotherapy has entered standard of care in the treatment of patients with metastatic melanoma. The infusion of autologous tumor-infiltrating T lymphocytes (TIL) is capable of mediating durable tumor regression and is now Food and Drug Administration-approved for patients with disease refractory to immune checkpoint inhibitors. Since the advent of chimeric antigen receptor (CAR) T cells for patients with hematological malignancies, a growing network of centers capable of delivering effector T cell products to patients has developed. Administration of TIL can be layered onto that institutional framework, but there are many complex and unique aspects to TIL immunotherapy. The highly multidisciplinary clinical expertise and coordination required to successfully and safely deliver TIL to patients began within the National Cancer Institute Surgery Branch and have been subsequently adopted worldwide. The general steps, most of which require hospital inpatient resources, include a surgical procedure to harvest sufficient tumor for TIL manufacturing, admission for non-myeloablative lymphodepleting chemotherapy followed by TIL, and intravenous interleukin-2 (IL-2, aldesleukin). Here, we provide the principles, practice, and required resources underlying the efficient and safe delivery of TIL immunotherapy derived from the clinical expertise of high-volume centers around the world. This article enhances published clinical practice guidelines by providing underlying clinical rationale and data-driven examples to demystify TIL immunotherapy in order to facilitate uptake and improve patient access to this promising treatment modality in clinical and research settings.

Keywords: Adoptive cell therapy - ACT; Cytokine; Immunotherapy; Surgery; Tumor infiltrating lymphocyte - TIL

DOI: https://doi.org/10.1136/jitc-2024-010207

J Transl Med. 2025 Jan 22. 23(1): 102

Application of adoptive cell therapy in malignant melanoma.

Qianrong Hu, Jiangying Xuan, Lu Wang, Kangjie Shen, Zixu Gao, Yuhong Zhou, Chuanyuan Wei, Jianying Gu.

Cutaneous melanoma is one of the most aggressive skin cancers originating from skin pigment cells. Patients with advanced melanoma suffer a poor prognosis and generally cannot benefit well from surgical resection and chemo/target therapy due to metastasis and drug resistance. Thus, adoptive cell therapy (ACT), employing immune cells with specific tumor-recognizing receptors, has emerged as a promising therapeutic approach to display on-tumor toxicity. This review discusses the application, efficacy, limitations, as well as future prospects of four commonly utilized approaches -including tumor-infiltrating lymphocytes, chimeric antigen receptor (CAR) T cell, engineered T-cell receptor T cells, and chimeric antigen receptor NK cells- in the context of malignant melanoma.

Keywords: Adoptive Cell Therapy; Chimeric Antigen Receptors (CARs)-T cell; Malignant Melanoma; Natural Killer (NK) Cells; T-cell Receptors; Tumor-infiltrating Lymphocytes

DOI: https://doi.org/10.1186/s12967-025-06093-2

ESMO Open. 2025 Jan 17. pii: S2059-7029(24)01891-X. [Epub ahead of print]10(2): 104120

Tumor-infiltrating lymphocytes in HER2-positive breast cancer: potential impact and challenges.

I Schlam, S Loi, R Salgado, S M Swain.

INTRODUCTION: In this review, we evaluate the role of stromal tumor-infiltrating lymphocytes (sTILs) as a biomarker in human epidermal growth factor receptor 2 (HER2)-positive breast cancer, exploring the prognostic and predictive potential in various treatment settings.
METHODS: Data from multiple clinical trials in the early and metastatic settings, focusing on TILs' correlation with pathologic complete response (pCR), progression-free survival (PFS), and overall survival across early and metastatic HER2-positive breast cancer were summarized. This review also discusses TILs' assessment methods, interobserver variability, and emerging technologies to assess TILs.
RESULTS: TILs have been identified as a highly reproducible biomarker that predicts pCR in patients receiving neoadjuvant therapy and serves as a prognostic indicator for long-term outcomes in several breast cancer subtypes, including HER2-positive. Studies indicate that higher TIL levels correlate with better recurrence-free survival rates. Despite these findings, there is no consensus on the optimal TIL threshold for clinical decision making, and further research is required on how to incorporate TILs into routine clinical practice.
CONCLUSIONS: TILs represent a promising biomarker in HER2-positive breast cancer, particularly in early disease settings. This assessment could guide treatment de-escalation or intensification, tailoring therapies to individual patient profiles. Due to their prognostic importance, TILs can be added to pathology reports. However, further validation in clinical trials is essential for the widespread adoption of TILs in clinical practice.

Keywords: HER2-positive breast cancer; biomarkers; neoadjuvant therapy; pathologic complete response; stromal tumor-infiltrating lymphocytes

DOI: https://doi.org/10.1016/j.esmoop.2024.104120

Mol Cancer Ther. 2025 Jan 24.

Co-blocking TIGIT and PVRIG using a novel bispecific antibody enhances anti-tumor immunity.

Yuan Lin, Kan Lin, Qiang Fu, Xing Sun, Huan Wang, Lu Su, Yinghui Xu, Cheng Liao.

TIGIT and PVRIG are immune checkpoints co-expressed on activated T and NK cells, contributing to tumor immune evasion. Simultaneous blockade of these pathways may enhance therapeutic efficacy, positioning them as promising dual targets for cancer immunotherapy. This study aimed to develop a bispecific antibody (BsAb) to co-target TIGIT and PVRIG. Expression of TIGIT and PVRIG was assessed on tumor-infiltrating lymphocytes (TILs) from patients with various cancers, including non-small cell lung cancer (n=63) and colorectal cancer (n=26). The BsAb was engineered by fusing anti-PVRIG nanobodies to the N terminus of anti-TIGIT antibodies. Functional characterization of the BsAb was performed in vitro and in vivo, including assessments of T and NK cell activation and cytotoxicity. Pharmacokinetics and safety profiles were evaluated in cynomolgus monkeys. Statistical analyses were conducted using the Student's t-test. The results showed that the BsAb effectively blocked TIGIT and PVRIG from binding their respective ligands, CD155 and CD112, leading to significant increases in T cell activation (2.8-fold, p<0.05) and NK cell cytotoxicity (1.8-fold, p<0.05). In vivo, the BsAb demonstrated potent anti-tumor activity, both as a monotherapy and in combination with anti-PD-1 or anti-PD-L1, in humanized PBMC and transgenic mouse models. Pharmacokinetic studies in cynomolgus monkeys revealed a favorable profile, with no dose-limiting toxicities observed after four repeated doses of 200 mg/kg. These findings provide compelling preclinical evidence for the therapeutic potential of targeting the TIGIT-PVRIG axis with a bispecific antibody. This approach shows promise for enhancing anti-tumor immunity and warrants further investigation in clinical trials.

DOI: https://doi.org/10.1158/1535-7163.MCT-23-0614

J Exp Med. 2025 Mar 03. pii: e20240776. [Epub ahead of print]222(2):

The XCL1-XCR1 axis supports intestinal tissue residency and antitumor immunity.

Amir Ferry, Kianoosh M Mempel, Alexander Monell, Miguel Reina-Campos, Nicole E Scharping, Maximilian Heeg, Kennidy K Takehara, Shiruyeh Schokrpur, Ning Kuo, Robert Saddawi-Konefka, J Silvio Gutkind, Ananda W Goldrath.

Tissue-resident memory T cells (TRM) provide frontline protection against pathogens and emerging malignancies. Tumor-infiltrating lymphocytes (TIL) with TRM features are associated with improved clinical outcomes. However, the cellular interactions that program TRM differentiation and function are not well understood. Using murine genetic models and targeted spatial transcriptomics, we found that the CD8+ T cell-derived chemokine XCL1 is critical for TRM formation and conventional DC1 (cDC1) supported the positioning of intestinal CD8+ T cells during acute viral infection. In tumors, enforced Xcl1 expression by antigen-specific CD8+ T cells promoted intratumoral cDC1 accumulation and T cell persistence, leading to improved overall survival. Notably, analysis of human TIL and TRM revealed conserved expression of XCL1 and XCL2. Thus, we have shown that the XCL1-XCR1 axis plays a non-cell autonomous role in guiding intestinal CD8+ TRM spatial differentiation and tumor control.

DOI: https://doi.org/10.1084/jem.20240776