Letter from the Editor | JITC Editor Picks | JITC at AACR 2025
40th Anniversary Series | Popular Archive Articles
Letter from the Editor
Hello JITC Readers,
I just returned from London with other Editors-in-Chief for the 76 journals (like ours) published by the BMJ Group. We focused on many issues that confront our knowledge workers in the modern era, including the use of multimedia, ethics, how to improve the quality of content and… the state of our world.
I was asked by many there to address what was happening politically in the U.S. Indeed, it is hard for any of us to fully understand and foresee the consequences of wholesale downsizing and reduction in force at the FDA, the NIH, the NSF, the CDC, and other U.S. federal institutions, and how those actions impact us and the rest of the world. Looking backwards, it is easy to consider this a ‘cultural revolution’, comparable to what happened in China for ten years during the period 1966-1976. The response then, in a largely isolated country, was to the bureaucratic obstacles that accompanied building a socialist state. Our current situation is quite different. The U.S. is clearly connected with the world. With xenophobia emerging all around us, we need to clearly define the province of science as borderless, and our Journal should continue to reflect this.
Although the U.S. has built up substantial governmental agencies that have served us well, the agencies are going through a major set of changes, hopefully to make them more efficient and effective. Still, the broader issues of the means to this end—and the loss of substantial talent and experience in our agencies—must give us pause as we drive the development of modern immunotherapies.
The primary purpose of our Journal is to provide curation, improvement, and dissemination of important information for our readers. To that end, I must say that this has been an amazing month with substantial and exciting findings that, for now, many of which have converged on the substantial ability of machine learning and artificial intelligence to help us consider the information overload that we have generated for ourselves and discern meaning. The articles selected for highlighting this month (below) come from around the world and are increasingly utilizing modern AI to help discern the edges and nodes of meaning in our datasets. They demonstrate a remarkable confluence of artificial and biological learning.
Before signing off, I encourage you to engage with our editors as they attend conferences throughout the world. We thrive on speaking with researchers about their work and how to take it to the next level through publication. If you are at the AACR 2025 meeting in Chicago, please consider stopping by the SITC booth (#2813) to attend the Meet-the-Editor session with JITC Section Editor Dr. Marcela Maus at 12:30pm CT on Monday, April 28th. We hope to see you there and at other future conferences.
Regards,
Michael T. Lotze, MD
Editor-in-Chief
Journal for ImmunoTherapy of Cancer
JITC Editor Picks
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Machine learning identifies clinical tumor mutation landscape pathways of resistance to checkpoint inhibitor therapy in NSCLC
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Summary:
Examining the response to therapy or resistance using multiple patients (n=4433) with non-small cell lung cancer could identify 33 genes associated with strong predictors of response with three identified prognostic markers. The authors took an interesting approach examining not only 'mutated' versus 'nonmutated' (binary, but also high-frequency vs low-frequency mutations), and the location of the mutations for their analysis. They confirmed the role of increased serum IL-6 as an adverse predictor of response to immune checkpoint blockade (ICB) as well as their previous observations of the roles of PDL1 and tumor mutational burden. They emphasized that there are no approved therapies to reverse some of the resistance mechanisms identified (such as WNT/beta catenin pathways, p38 mutations, KRAS mutations, or FGFR2 mutations). These changes further link tumor mutations with resistance to ICB and will need to be linked to deep measures of clonality/Gini-Simpson indices of the adaptive immune response in the future.
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Identification of a conserved subset of cold tumors responsive to immune checkpoint blockade
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Borcellos-Hoff and colleagues identified an unusual group of patients across various histologies whose tumors were low in transforming growth factor-beta (TGFβ) signaling signatures and yet had defects in DNA mismatch repair in a combined βALT score. In murine models, they demonstrated that irradiation and TGFβ inhibition could enhance response to ICB. Furthermore, NK cell infiltration was associated with increased immune responses in their murine models and predicted response to ICB in patients.
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Society for Immunotherapy of Cancer (SITC) consensus statement on essential biomarkers for immunotherapy clinical protocols
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Summary:
The SITC Clinical Immuno-Oncology Network (SCION) represents a particularly promising program that brings physicians and non-physicians, from industry and academe, to work in small groups and faculty on a clinical IO proposal. One outcome of this now five-year-old program has been the focus on early phase clinical trials and which biomarkers should be considered in the modern era as essential to be measured. This manuscript was the consequence of an initial Delphi survey of SITC members and JITC readership. Potential 'essential' markers under consideration include tertiary lymphoid structures, MHC Class I expression, and clonality/Gini Score of T and B cells within the tumor. Further efforts will undoubtedly rely increasingly on ML/AI strategies.
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New Special Series: SITC 40th Anniversary: I-O Progress and Potential