Blogs

Non-invasive multimodal CT deep learning biomarker to predict pathological complete response of non-small cell lung cancer following neoadjuvant immunochemotherapy: a multicenter study

Guanchao Ye, Guangyao Wu, Yu Qi, Kuo Li, Mingliang Wang, Chunyang Zhang, Feng Li, Leonard Wee, Andre Dekker, Chu Han, Zaiyi Liu, Yongde Liao, Zhenwei Shi
Journal for ImmunoTherapy of Cancer 2024;12:e009348 (3 September 2024)
RESEARCH

Summary:

Neoadjuvant treatment with immunochemotherapy in patients with non-small cell lung cancer (NSCLC) has demonstrated improved survival outcomes and increased pathological complete response (pCR) rates. Methods of predicting or assessing pCR that are non-invasive would be extremely valuable to both patients and physicians. In this study, the authors developed an AI-based prediction model that extracts deep learning features from pretreatment multimodal (contrast enhanced and non-contrast enhanced) computed tomography (CT) scans to predict pCR in patients with NSCLC who are receiving neoadjuvant immunochemotherapy. The performance of a combined model (LUNAI-fCT), fused from two separate predictive models, was evaluated using retrospective CT scans from 112 patients and resulted in an accuracy of 0.800, sensitivity of 0.917, specificity of 0.739, and an area under the receiver operating characteristic curve (AUC) of 0.866, improving on other predictive models. The integration of AI-based prediction models, such as the one developed here, into routine assessment of pretreatment imaging will help guide treatment decisions in a non-invasive manner, which will improve patient quality of life. 

S100A9 and HMGB1 orchestrate MDSC-mediated immunosuppression in melanoma through TLR4 signaling

Feyza Gül Özbay Kurt, Beatrice-Ana Cicortas, Bianca M Balzasch, Carolina De la Torre, Volker Ast, Ece Tavukcuoglu, Cagla Ak, Sebastian A Wohlfeil, Adelheid Cerwenka, Jochen Utikal, Viktor Umansky
Journal for ImmunoTherapy of Cancer 2024;12:e009552 (11 September 2024)
RESEARCH

Summary:

Resistance to immune checkpoint blockade (ICBs) remains a significant problem for many patients with melanoma, with myeloid-derived suppressor cells (MDSCs) likely contributing to this resistance through the immunosuppression of activated T cells. Damage-associated molecular pattern molecules (DAMPs), including S100A8, S100A9, and high mobility group Box 1 (HMGB1), have been implicated in the activation of MDSCs through their interaction with toll-like receptor 4 (TLR4) and the receptor for advanced glycation end-products (RAGE), however, these interactions are still poorly defined. This study sought to investigate the role of these DAMPs and their influence on MDSC activation. The investigators found that treatment of healthy, donor-derived monocytes in vitro with S100A9 and HMGB1 resulted in significant T cell suppression, which was blocked when TLR4 and S100A9 inhibitors were added to the co-culture. Single-cell RNA sequencing of monocytes isolated from patients with melanoma revealed increased expression of S100 genes and other genes associated with MDSC development. These findings further define the roles of S100A8/9, HMGB1, TLR4, and RAGE in the conversion of monocytes into MDSC-like cells, expanding the possibilities for potential targets in future immunotherapy development and biomarker discovery.

Regression of renal cell carcinoma by T cell receptor-engineered T cells targeting a human endogenous retrovirus

Stefan Barisic, Elizabeth M Brahmbhatt, Elena Cherkasova, Timothy T Spear, Ujjawal Savani, Stephanie Pierre, Gina M Scurti, Long Chen, Muna Igboko, Rosa Nadal, Gang Zeng, Gordon Parry, David F Stroncek, Steven Highfill, Annika V Dalheim, Robert Reger, Michael I Nishimura, Richard W Childs
Journal for ImmunoTherapy of Cancer 2024;12:e009147 (11 September 2024)
RESEARCH

Summary:

Human endogenous retroviruses (HERVs) offer unique antigen targets for immunotherapies, such as engineered T cell receptor T cells (TCR-T). A novel HERV (CT-RCC HERV-E), selectively expressed in most clear cell renal cell carcinomas (ccRCC), has shown promising potential as an immunotherapy target. This preclinical study evaluated the anti-tumor activity of a TCR-T cell clone (HERV-E T cells) that targets an HLA-A11-restricted peptide derived from CT-RCC HERV-E. The HERV-E T cells caused potent in vitro cytolysis of HLA-A11⁺ ccRCC cells expressing CT-RCC HERV-E that was not observed in knockout (KO) models (HERV-E KO and β2 microglobulin KO) or wildtype HLA-A11^- ccRCC cells. In a xenograft mouse model, HERV-E T cell infusion of NSG male mice that were inoculated with HLA-A11⁺ HERV-E⁺ ccRCC cells induced significant tumor regression and led to improved survival in comparison to controls. The detailed characterization of this novel TCR-T cell clone and subsequent successful display of anti-tumor activity in a xenograft mouse model has served as the foundation for clinical studies in patients with metastatic ccRCC, which are initiating now.

Anti-metabolite chemotherapy increases LAG-3 expressing tumor-infiltrating lymphocytes which can be targeted by combination immune checkpoint blockade

Nicola Principe, Amber-Lee Phung, Kofi L P Stevens, Omar Elaskalani, Ben Wylie, Caitlin M Tilsed, Fezaan Sheikh, M Lizeth Orozco Morales, Joel Kidman, Elly Marcq, Scott A Fisher, Anna K Nowak, Alison M McDonnell, W Joost Lesterhuis, Jonathan Chee
Journal for ImmunoTherapy of Cancer 2024;12:e008568 (28 September 2024)
RESEARCH

Summary:

Immune checkpoint blockade (ICB) is approved and implemented in a variety of malignant disease states.

Response to ICB, however, can be variable and is often dependent on the frequency and distribution of progenitor exhausted CD8⁺ T cells (T_PEX). Combinations of ICB with chemotherapy have been effective treatme

nt strategies, but it is unclear how chemotherapy alters T_PEX frequency and gene expression. This work investigated the impact of sequential chemotherapy on T_PEX frequency and expression of immune checkpoint surface proteins in multiple murine tumor models. Two doses of anti-metabolite chemotherapy significantly increased the frequency of tumor infiltrating CD4⁺ and CD8⁺ T_PEX cells expressing lymphocyte activating gene-3 (LAG-3). Combining chemotherapy with anti-LAG-3 and/or anti-PD-1 treatment led to improved survival and anti-tumor response in comparison to each agent alone. These findings demonstrate the utility of combining chemotherapy with ICB, connecting the improved response to the corresponding changes in T_PEX frequency and gene expression after chemotherapy.

2024 Pedro J. Romero Service to JITC Award
Congratulations to Andrea Kunz, the recipient of this year’s Pedro J. Romero Service to JITC Award. Nominated and selected by SITC in recognition of her outstanding dedication to the journal, she has served as JITC’s Managing Editor since 2016. Dutifully carrying out the vision and culture of the journal, Ms. Kunz’s impact has been commensurate with the growth and success of JITC.
 

Andrea Kunz
Society for Immunotherapy of Cancer

2024 JITC Best Paper Award Recipients
The JITC Best Paper Awards celebrate excellence in scientific research and are awarded to researchers demonstrating leadership in the field as well as innovation and high-quality execution and discussion in their manuscripts and are nominated by JITC’s Editorial Board. Congratulations to the 2024 JITC Best Paper Award recipients.
 

Basic Tumor Immunology
Siyu Zhang; Wenbei Peng, PhD; Haolei Wang, PhD; Xuan Xiang – Huazhong University of Science and Technology (China)
C1q⁺ tumor-associated macrophages contribute to immunosuppression through fatty acid metabolic reprogramming in malignant pleural effusion 

Clinical/Translational Cancer Immunotherapy
Jun Masuda, MD – The Cancer Institute Hospital of Japanese Foundation for Cancer Research (Japan)
Efficacy, safety, and biomarker analysis of nivolumab in combination with abemaciclib plus endocrine therapy in patients with HR-positive HER2-negative metastatic breast cancer: a phase II study (WJOG11418B NEWFLAME trial)

Immune Cell Therapies and Immune Cell Engineering
MacLean S. Hall, PhD – H. Lee Moffitt Cancer Center and Research Institute (USA)
Neoantigen-specific CD4⁺ tumor-infiltrating lymphocytes are potent effectors identified within adoptive cell therapy products for metastatic melanoma patients

Immunotherapy Biomarkers
Bettzy Stephen, MBBS – University of Texas MD Anderson Cancer Center (USA)
T-cell receptor beta variable gene polymorphism predicts immune-related adverse events during checkpoint blockade immunotherapy

Oncolytic and Local Immunotherapy
Fadi Azar – Transgene SA (France)
TG6050, an oncolytic vaccinia virus encoding interleukin-12 and anti-CTLA-4 antibody, favors tumor regression via profound immune remodeling of the tumor microenvironment

APC Discounts

As a way to thank the SITC members who work tirelessly to advance the science and improve the lives of cancer patients, SITC will provide members with a 35% discount on Article Processing Charges (APCs) for all accepted JITC articles submitted in 2024. This discount is applied post-acceptance, at which point a discount code is shared with the corresponding author.

Become a SITC Member Today!

JITC also offers full waivers for the full APC (100% discount of the APC) where all authors are based in low-income countries (see policy). Requests for waivers must be made prior to submission. For additional information regarding these discounts, as well as institutional arrangements and editor/reviewer discounts, view the journal's APC policy. Additional questions may be directed to JITCEditor@sitcancer.org.