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Letter from the Editor| JITC  Editor Picks|2025  JITC  Mentorship Graduates|Popular Archive Articles

Letter from the Editor

Hello  JITC
  Readers,

 It has been a busy period again in IO, with numerous conferences taking place in recent weeks. This past month I attended the 40^th Society for Immunotherapy of Cancer Annual Meeting in National Harbor, MD, and also had a chance to develop a session on “Imaging, Radiomics, and Integrated Biomarkers” as Co-Chair with Wim Vos, MSc, PhD. Shown is the meeting with the JITC Best Paper recipients for Immune Cell Therapies and Immune Cell Engineering, Javier Arroyo-Ródenas, PhD, and Aïda Falgàs Comamala, PhD, at the Meet-the-Editor session. Their paper, “CD22 CAR-T cells secreting CD19 T-cell engagers for improved control of B-cell acute lymphoblastic leukemia progression,” continues the theme of delivering novel constructs to the TME by immune cells including bispecifics and cis-cytokines.

Kudos to my colleague and JITC Deputy Editor-in-Chief, Sjoerd van der Burg, PhD, for his Pedro J. Romero Service to JITC Award. Other exciting aspects of the SITC meeting for me included the remarkable results presented on in vivo CAR T constructs enabling, without nonmyeloablative chemotherapy, complete responses in patients with multiple myeloma.

The impressive biennial presentations from this, the 6^th World Immunotherapy Council (WIC), were also engaging. The WIC now constitutes 27 separate international groups spanning the continents. Special kudos to organizers Cheng Sun, MD, PhD, University of Science and Technology of China; Rieneke van de Ven, PhD, Amsterdam University Medical Centers; and Joe Yeong, MD, PhD, Singapore General Hospital. The Alliance for Cancer Gene Therapy (ACGT) also held their annual luncheon at SITC with a fireside chat with Carl June, MD, along with ACGT board member Marc Engelsgjerd, MD. The major issue about limiting the regulation of novel first-in-human studies as well as the emergence and oversight of in vivo CRISPR screens were discussed. Last but not least, after 25 years of service to SITC, the remarkable Tara Withington celebrated her upcoming retirement and bid us farewell with plenty of fanfare, tears, and hugs.

I also attended the Upstate New York Immunology Conference in Oswego, NY, nestled on the shore of Lake Ontario, October 27–30, 2025. Like other regional immunology meetings (the Autumn Immunology Conference in the Midwest and the Translational Research Cancer Center Conference held in the winter among mid-Atlantic institutions), this one allows for detailed oral and poster presentations by graduate students and postdocs. Dario Vignali, PhD, Chair of Immunology at the University of Pittsburgh, gave the keynote after the opening dinner on “LAG3: The Third Checkpoint Inhibitor & its Synergistic Interactions with PD1.” Although other checkpoints mechanisms converge on the second signal CD28, much of the biology of LAG3 appears to limit signal one and TCR signaling. Indeed, LAG3 homodimers bind the TCR-CD3 complex, inhibiting signaling. There is still much to learn about how this molecule affects T cell function and migration as well as recent findings of ubiquitination to enhance its function. 

This has been a difficult period in biotechnology with capital markets limited and many cell therapy companies closing their doors or pivoting to autoimmunity. The 7^th Annual TIL Therapies Summit, held November 11–13 in Boston, provided additional enthusiasm for the field. Highlighted were drug-enhanced and genetically engineered TIL with early evidence of biologic mechanisms and clinical activity. The meeting brought together investigators from the local Harvard ecosystem as well as from Obsidian, KSQ, GRIT, ScaleReady, and ThermoFisher among other companies. Particularly intriguing to me was a new startup from France, Carmil Therapeutics, providing another means to largely overcome the need for CD28 costimulation with a CARMIL2 gain-of-function mutation, a critical need for emergent TIL therapies.

This month, in part prompted by the approval of LAG3 blockade in combination with PD-1 blockers, we will focus on the international efforts to extend immune checkpoint blockade in the clinic. See these highlights and more in my editor selections below!

Regards, 

Michael T. Lotze, MD
Editor-in-Chief
Journal for ImmunoTherapy of Cancer

JITC Editor Picks

Abscopal effects in patients with malignant melanoma treated with radiotherapy and immune checkpoint inhibition: analysis of a large observational multicenter study

Summary:

The vast preponderance, and likely all conventional radiation therapy (CRT) protocols in combination with immune checkpoint blockade (ICB), have failed to demonstrate additional benefit. Now, with an effort to make radiation therapy an immunotherapy itself and in combination, stereotactic body radiotherapy (SBRT) has begun to show some signs of effectiveness. In this study from 12 cancer centers in Germany, 3773 melanoma patients were retrospectively identified and 47 identified having received radiation therapy (largely to the brain or lung) following ICB. In these individuals who received SBRT as opposed to CRT, ‘abscopal’ benefit was observed with increased overall and progression-free intervals, prompting a call for a prospective study, which seems warranted. Although lactate dehydrogenase as an essential biomarker was measured, neutrophil-to-lymphocyte ratios were not provided nor other immune measures. Just as dose, route, and schedule have been important parameters for defining other oncologic therapies, we now in the era of IO find ourselves knowing that CRT drives lymphopenia much more than SBRT and asking ourselves how to more effectively deliver SBRT as an immunotherapy.

Pharmacokinetics and safety of subcutaneous nivolumab: results from the phase I/II CheckMate 8KX study

Summary:

As we are now 15 years into intravenous therapies with ICB, we see in addition to the plethora of PD-1/VEGF bispecifics being tested in the clinic, the emergence and approval of subcutaneous ICB with nivolumab tested with and without recombinant human hyaluronidase PH20 (rHuPH20). This was tested in Italy in CheckMate 8KX in a variety of regimens and various tumor types. After 147 patients were enrolled, 103 patients were treated on various single-cycle regimens converging to 36 patients receiving 1200 mg of nivolumab administered in combination with the hyaluronidase subcutaneously every four weeks. Peak antibody levels were observed in the serum at 5-7 days and without apparent emergence of neutralizing antibodies. Increased CD8⁺ T cells were found as a percentage with increased PDL1⁺ expression on biopsy, increased mean sPD-1 and IFN gamma in the serum. Gamma interferon levels diminished over time and with continued treatment. This approval allows for a more convenient option for patients.

Perioperative pembrolizumab in early-stage non-small cell lung cancer (NSCLC): conventional and distribution-based immune profiling of the tumor microenvironment and peripheral circulation

Summary:

This study from Duke had already reported important clinical results with apparently the baseline PD-L1 tumor proportion score trending to be associated with increased survival but not meeting significance. Here, the authors took a ‘distribution’ rather than frequency-based analysis of the TME with detailed assessment of the peripheral blood mononuclear cells on banked specimens. In the peripheral blood, decreased GZMB and increased CD127 and CD28 in the CD8⁺ T cells were associated more frequently with major pathologic response in these resectable non-small cell lung cancer patients. This in part was thought to represent a pre-exhausted state amenable to ICB. Detailed analysis of the baseline biopsies on CD8⁺, CD45RA⁺ CD197⁺(CCR7) showed that low expression of KLRG1 and GrzB was also associated with major pathologic response. These pre-exhausted cells were thought to potentially only be functional in the presence of CD28. When examining both the baseline and resected specimens pathologically, the presence of CD197 expression on CD8, CD39 dual positive cells as well as CD38 expression in the CD8⁺ T cells and CD8⁺CD366 (TIM3) dual positive cells were most predictive of response. Although this detailed analysis may be useful in identifying patients most likely to respond, it also adds to the deeper understanding of the biology of immune cells that needs greater attention. Notable, in its absence, was a deep analysis of the myeloid cells, including the important BatF3, CD103⁺ cDC1s, critical for T cell persistence and function. Still, the application of neoadjuvant immunotherapies is serving to enlighten us about the most effective strategies for patients with earlier disease.

Cadonilimab combined with taxane and cisplatin as the first-line treatment of advanced esophageal squamous cell carcinoma: an open-label, multicenter phase II trial

Summary:

Esophageal cancer is the 6^th in incidence and 4^th as a cause of cancer-related deaths in China. 43 patients were treated on a bispecific antibody, cadonilimab, that was Fc-null and targeted both PD-1 and CTLA-4 in combination with administration of a taxane and cisplatin. The overall response rate was quite impressive with 81.4% response in patients with a PD-1 combined positive score (CPS) of >10 in 39.5% of patients. Sadly, the median progression-free survival (PFS) was only 7.1 months in this group of patients. Hypomethylation of several sites known to be associated with regulating immune responsiveness (APBA2, EPAS1, TRIM58, ITPKA and LINC00554 genes) was observed more in the responders than the nonresponders, suggesting another putative biomarker for assessment in IO. This compares well with the late follow up of the ESCORT-1st study (NCT03691090) that tested an anti-PD1 antibody, camrelizumab, to first-line chemotherapy in untreated advanced or metastatic esophageal squamous cell carcinoma patients. The investigator-assessed objective response rate was only 72.1% but with a comparable median PFS of 7.6 months (95% CI 6.9–8.3).

2025 JITC Peer Review Mentorship Program Graduates

Congratulations to the JITC Peer Review Mentorship Program Graduates who completed the 2025 program, reviewing manuscripts with their mentors January-September:

Michał Abendrot, PharmD Ahdab Alsaieedi, PhD Hampus Andersson, PhD Tobias Bexte, MD Akash Boda, PhD Apoorvi Chaudhri, PhD Paolo Davide d'Arienzo, MD

Kristen Fousek, PhD Beatriz German Falcon, PhD Jaeseung Hahn, PhD Ogur Karhan, PhD Debbie Ledezma, PhD Juyeun Lee, PhD Maher Nawaf, PhD

Ditsa Sarkar, PhD Sejal Sharma, MS Karina Suchowski, PhD Mala Talekar, MBBS Aleksei Tikhonov, PhD Jan Zaucha, PhD

JITC also sends its sincere gratitude and appreciation to the 2025 mentors for their generous time and commitment to the program, providing structural guidance on peer review:

Praveen Bommareddy, PhD Alessio Cortellini, MD, PhD Julia Cuende, PhD Oliver Kepp, PhD

Il Minn, PhD Paola Nistico, MD Walter Storkus, PhD Pierosandro Tagliaferri, MD

Learn more about the Peer Review Mentorship Program and how to become a volunteer reviewer for JITC.

Popular Archive Articles

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.

Localization and density of tertiary lymphoid structures associate with molecular subtype and clinical outcome in colorectal cancer liver metastases  
(9 February 2023) 
RESEARCH

Tryptophan depletion sensitizes the AHR pathway by increasing AHR expression and GCN2/LAT1-mediated kynurenine uptake, and potentiates induction of regulatory T lymphocytes (21 June 2023) 
RESEARCH

The NR_109/FUBP1/c-Myc axis regulates TAM polarization and remodels the tumor microenvironment to promote cancer development  (22 May 2023) 
RESEARCH

B cells and the coordination of immune checkpoint inhibitor response in patients with solid tumors  (16 April 2024) 
REVIEW 

Don’t Forget to Check Out These Other Great JITC Special Series:
Cancer Immunotherapy in Understudied Populations (2024-2025)
Computational Immuno-Oncology (2023-2025)
Liquid Biopsies (2022-2023)

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 members who are first, last, or corresponding authors on JITC articles at the time of acceptance will receive discounted Article Processing Charges (APCs) . This discount is applied post-acceptance, at which point a discount code is shared with the corresponding author. Learn more .

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 JITC Editor@sitcancer.org.