Blogs

Hybrid epithelial-mesenchymal status of lung cancer dictates metastatic success through differential interaction with NK cells

Monica Parodi, Giovanni Centonze, Fabio Murianni, Paola Orecchia, Francesca Andriani, Ilaria Roato, Cecilia Gardelli, Melissa Balsamo, Massimo Moro, Giulia Taiè, Ugo Pastorino, Andrea Petretto, Chiara Lavarello‎, Massimo Milione, Gabriella Sozzi, Luca Roz, Massimo Vitale, Giulia Bertolini
Journal for ImmunoTherapy of Cancer 2024;12:e007895 (7 March 2024)

RESEARCH

Summary:

This study examined the pro-metastatic mechanics of non-small cell lung cancer (NSCLC) cells that undergo epithelial to mesenchymal transition (EMT). EMT exhibits three primary cellular states – epithelial (E), hybrid (H), and mesenchymal (M). Human lung cancer cell lines representing E, M, and H states were analyzed for their phenotypic properties, dissemination capabilities, and natural killer (NK) cell interactions. H-cells were found to have limited dissemination capabilities but expressed low levels of NK-cell attracting chemokines and increased B7-H3, an NK cell inhibitory ligand. Patient sample analysis validated these observations, showing that samples with H-cell phenotype were associated with low NK cell infiltration in NSCLC and poorer prognosis. These data demonstrated that H-cells play a role in metastatic spread in NSCLC by avoiding NK cell attraction and infiltration into metastatic tumor sites. These mechanistic findings may provide targets for future therapeutic interventions.

Digital spatial proteomic profiling reveals immune checkpoints as biomarkers in lymphoid aggregates and tumor microenvironment of desmoplastic melanoma

David G Su, David A Schoenfeld, Wael Ibrahim, Raysa Cabrejo, Dijana Djureinovic, Raymond Baumann, David L Rimm, Sajid A Khan, Ruth Halaban, Harriet M Kluger, Kelly Olino, Anjela Galan, James Clune
Journal for ImmunoTherapy of Cancer 2024;12:e008646 (21 March 2024)

RESEARCH

Summary:

Digital spatial proteomic profiling is an effective way to differentiate cellular subsets within a heterogeneous tissue environment. The investigators used this technology to examine 45 patient histology samples of desmoplastic melanoma (DM) collected between 1989 and 2018. DM is a rare subtype of cutaneous melanoma that contains a unique tumor microenvironment which results in an inability to use prognostic tools and treatment decisions designed for conventional melanoma. With this analysis, DM was able to be separated between pure and mixed populations based on immune checkpoint markers. Data also showed that lymphoid aggregates that showed high expression of LAG-3 and PD-1 were associated with worse overall survival and shorter recurrence-free survival, respectively. These data have demonstrated that proteomic immunoprofiling has the potential to improve clinical distinction between the histological subtypes of DM. Further studies will validate the initial biomarker findings in this study.

Impact of immunotherapy time-of-day infusion on survival and immunologic correlates in patients with metastatic renal cell carcinoma: a multicenter cohort analysis

Jimmy S Patel, Yena Woo, Amber Draper, Caroline S Jansen, Jennifer W Carlisle, Pasquale F Innominato, Francis A Lévi, Layla Dhabaan, Viraj A Master, Mehmet A Bilen, Mohammad K Khan, Michael C Lowe, Haydn Kissick, Zachary S Buchwald, David C Qian
Journal for ImmunoTherapy of Cancer 2024;12:e008011 (26 March 2024)

RESEARCH

Summary:

There is growing preclinical evidence that the adaptive immune response is most effectively stimulated earlier in the day. As such, recent studies in patients with metastatic melanoma or non-small cell lung cancer demonstrate an association between an earlier time-of-day infusion of immune checkpoint inhibitor (ICI) therapy and longer progression-free survival (PFS) and overall survival (OS). This study examined the same association in patients with metastatic renal cell carcinoma by analyzing records of patients with a univariate and multivariable Cox proportional hazards regression analysis. Results showed that patients in the group who received >20% of their ICI infusions before noon had a longer PFS and OS compared to the patients in the group who received <20% of their infusions before noon. These data further contribute to the growing association between earlier in the day ICI infusion and better outcomes for patients with cancer.

Cost-effectiveness of treating advanced melanoma with tumor-infiltrating lymphocytes based on an international randomized phase 3 clinical trial

Renske M T ten Ham, Maartje W Rohaan, Inge Jedema, Rob Kessels, Wim Stegeman, Walter Scheepmaker, Bastiaan Nuijen, Cynthia Nijenhuis, Melanie Lindenberg, Troels Holz Borch, Tine Monberg, Marco Donia, Inge Marie Svane, Wim van Harten, John Haanen, Valesca P Retel
Journal for ImmunoTherapy of Cancer 2024;12:e008372 (26 March 2024)

RESEARCH

Summary:

The investigators sought to perform a cost-utility analysis (CUA) in the Netherlands and Denmark on a novel cellular therapy known as tumor-infiltrating lymphocyte (TIL) therapy. This phase III, open-label, randomized clinical trial (NCT02278887) was a CUA comparing TIL-NKI/CCIT to standard of care treatment ipilimumab in patients with unresectable stage IIIC–IV melanoma after failure of first-line or second-line treatment. A Markov decision model compared expected costs of treatment and quality-adjusted life years (QALYs). Results showed that in the Netherlands, the mean total undiscounted lifetime benefits were 4.47 lifeyears (LYs) and 3.52 QALYs in TIL-NKI/CCIT therapy compared to 3.33 LYs and 2.46 QALYs for ipilimumab treatment. The same trend was observed in the Danish population. This CUA showed a benefit to TIL-NKI/CCIT therapy over ipilimumab, and as a result TIL-NKI/CCIT has been included as insured care and added to treatment guidelines in the Netherlands and Denmark.

As Incoming JITC Editor-in-Chief Michael T. Lotze, MD has been preparing and transitioning into his new role, the journal has had the unique opportunity to get to know him and ask such tried and true questions as, “How many marathons can one person possibly run?” Rather than keep these interactions behind closed doors, we conducted an open interview on everything from career inspirations to personal hobbies to help connect our readers with JITC’s next leader. Whether you would like to get to know him or you would like to test how well you already know him, check out our recent interview with Dr. Lotze.

The selections below represent some of the most popular content published in JITC over the past two years. Explore additional thematic content in JITC's Collections or access the rest of JITC's archives for a look at all the journal has to offer.

Single-cell transcriptome analysis revealed a suppressive tumor immune microenvironment in EGFR mutant lung adenocarcinoma
Lei Yang, Yun-Ting He, Song Dong, Xue-Wu Wei, Zhi-Hong Chen, Bo Zhang, Wei-Dong Chen, Xiao-Rong Yang, Fen Wang, Xue-Meng Shang, Wen-Zhao Zhong, Yi-Long Wu, Qing Zhou
Journal for ImmunoTherapy of Cancer 2022;10:e003534 (9 February 2022)
RESEARCH

TIGIT-CD226-PVR axis: advancing immune checkpoint blockade for cancer immunotherapy
Eugene Y Chiang and Ira Mellman
Journal for ImmunoTherapy of Cancer 2022;10:e004711 (4 April 2022)
REVIEW

Efficacy and safety of lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in patients with advanced melanoma after progression on immune checkpoint inhibitors and targeted therapies: pooled analysis of consecutive cohorts of the C-144-01 study
Jason Chesney, Karl D Lewis, Harriet Kluger, Omid Hamid, Eric Whitman, Sajeve Thomas, Martin Wermke, Mike Cusnir, Evidio Domingo-Musibay, Giao Q Phan, John M Kirkwood, Jessica C Hassel, Marlana Orloff, James Larkin, Jeffrey Weber, Andrew J S Furness, Nikhil I Khushalani, Theresa Medina, Michael E Egger, Friedrich Graf Finckenstein, Madan Jagasia, Parameswaran Hari, Giri Sulur, Wen Shi, Xiao Wu, Amod Sarnaik
Journal for ImmunoTherapy of Cancer 2022;10:e005755 (13 December 2022)
RESEARCH

Tuned activation of MSLN-CAR T cells induces superior antitumor responses in ovarian cancer models
Esther Schoutrop, Thomas Poiret, Ibrahim El-Serafi, Ying Zhao, Rui He, Alina Moter, Johan Henriksson, Moustapha Hassan, Isabelle Magalhaes, Jonas Mattsson
Journal for ImmunoTherapy of Cancer 2023;11:e005691 (6 February 2023)
RESEARCH

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 JITC articles submitted and accepted through 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.