Blogs

Welcome to the latest JITC Digest. June is Cancer Immunotherapy Month^TM and an opportunity to help promote awareness of the cancer immunotherapy field. I encourage you to learn more about how SITC celebrates the month and consider taking part in the educational and professional development opportunities offered by the society, including numerous upcoming events.

One important aspect of immunotherapy as it becomes standard of care in an increasing number of disease states are the position papers and guidelines that provide guidance to enhance clinical decision making in the field. View the collection of these articles that includes SITC’s clinical practice guidelines and feature two brand new publications offering guidance for treating gynecologic and gastrointestinal cancers.

In addition to these important guidelines, JITC continues to publish top-notch research, some of which are found in my Editor’s Picks below. Highlights include how the antidiabetic drug metformin directly improved CD8 T-cell fitness in hypoxia, both in vitro and in vivo by Finisguerra et al, and how a radiomics model provided an innovative and accurate way to predict the response of immune checkpoint inhibitors for patients with advanced breast cancer from Zhao et al.

Finally, regardless of the month, JITC is dedicated to providing authors with the best service possible. Our publisher, BMJ, has been rolling out changes to help improve the experience for authors. Learn about some of these tools in the special feature below.

JITC Editor Picks

ANDROGEN RECEPTOR BLOCKADE RESISTANCE WITH ENZALUTAMIDE IN PROSTATE CANCER RESULTS IN IMMUNOSUPPRESSIVE ALTERATIONS IN THE TUMOR IMMUNE MICROENVIRONMENT

The authors used RNA sequencing and interference, PCR, western blot, and co-culturing techniques to determine how human and murine prostate cancer cells chronically exposed to increasing concentrations of enzalutamide developed resistance to immune checkpoint blockade. They discovered suppression of immune signaling pathways (including IFN-gamma response signaling) and chemotaxis, decreased CD8⁺ T-cell populations, and increased monocytic myeloid-derived suppressor cell populations and PD-L1 expression in enzalutamide-resistant cells. These findings suggest that enzalutamide-resistant (and perhaps abiraterone-resistant) prostate cancer is immunosuppressed despite an upregulation of PD-L1 expression, blunting the response to anti-PD-1/anti-PD-L1 treatment in these patients.

METFORMIN IMPROVES CANCER IMMUNOTHERAPY BY DIRECTLY RESCUING TUMOR-INFILTRATING CD8 T LYMPHOCYTES FROM HYPOXIA-INDUCED IMMUNOSUPPRESSION

Research

Summary:

The authors exposed CD8 T-cells to hypoxia and metformin and administered metformin to hypoxic tumor-bearing mice receiving adoptive tumor-specific CD8 T-cell therapy (ACT) or immune checkpoint inhibitors to determine if metformin could amelioriate hypoxia-induced T-cell apoptosis and dysfunction in vitro and in vivo. Although metformin did not decrease tumor hypoxia, it did inhibit mitochondrial complex I and reduce reactive oxygen species, which in turn rescued CD8 T-cells from hypoxia-induced apoptosis, increased CD8 T-cell proliferation and cytokine production, and blunted PD-1 and LAG3 gene upregulation. Metformin combined with ACT or anti-PD-1 therapy reduced tumor growth, demonstrating a strategy to improve the efficacy of these therapies by improving CD8 T-cell fitness despite a hypoxic environment.

RADIOMIC AND CLINICAL DATA INTEGRATION USING MACHINE LEARNING PREDICT THE EFFICACY OF ANTI-PD-1 ANTIBODIES-BASED COMBINATIONAL TREATMENT IN ADVANCED BREAST CANCER: A MULTICENTERED STUDY

Summary:

The authors retrospectively analyzed clinical and computed tomography characteristics of training and validation patient cohorts to create a model to predict response of advanced breast cancer to anti-PD-1-based immune checkpoint inhibitor therapy. Predictive components including lines of previous therapy and visceral and tumor metastases were combined with molecular subtype to construct the clinical model, while a multilayer perceptron algorithm was used to select the most predictive radiomics features. The radiomics model, which successfully identified 98.2% (training cohort) and 100% (validation cohort) of patients with non-response, outperformed the clinical model (and had AUC values that did not differ significantly from the combination clinical-radiomics model).

CELL SURFACE MARKER-BASED CAPTURE OF NEOANTIGEN-REACTIVE CD8+ T-CELL RECEPTORS FROM METASTATIC TUMOR DIGESTS

Summary:

The authors directly isolated CD8⁺ T-cells co-expressing cell surface PD-1, CD39, and TIGIT from five digested, metastatic human epithelial tumors to capture neoantigen-reactive T-cell receptors. This method had 39.5% specificity and a median of 20.9% enrichment for neoantigen activity across all patients. Although fast and reliable with unique advantages over a transcriptomic approach, dominant clones produced from this method of TCR isolation were terminally differentiated and unable to survive traditional in vitro expansion.

Popular Archive Articles

The selections below represent some of the most popular content published in JITC over the past few 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.

RECOMMENDATIONS FOR STANDARDIZING BIOPSY ACQUISITION AND HISTOLOGICAL ASSESSMENT OF IMMUNE CHECKPOINT INHIBITOR-ASSOCIATED COLITIS

Christopher Ma, Rish K Pai, David F Schaeffer, Jonathan Krell, Leonardo Guizzetti, Stefanie C McFarlane, John K MacDonald, Won-Tak Choi, Roger M Feakins, Richard Kirsch, Gregory Y Lauwers, Reetesh K Pai, Christophe Rosty, Amitabh Srivastava, Joanna C. Walsh, Brian G Feagan, Vipul Jairath
Journal for ImmunoTherapy of Cancer 2022;10:e00456 (16 March 2022)
POSITION ARTICLE AND GUIDELINE

SOCIETY FOR IMMUNOTHERAPY OF CANCER (SITC) CLINICAL PRACTICE GUIDELINE ON IMMUNOTHERAPY FOR THE TREATMENT OF LUNG CANCER AND MESOTHELIOMA

Ramaswamy Govindan, Charu Aggarwal, Scott J Antonia, Marianne Davies, Steven M Dubinett, Andrea Ferris, Patrick M Forde, Edward B Garon, Sarah B Goldberg, Raffit Hassan, Matthew D Hellmann, Fred R Hirsch, Melissa L Johnson, Shakun Malik, Daniel Morgensztern, Joel W Neal, Jyoti D Patel, David L Rimm, Sarah Sagorsky, Lawrence H Schwartz, Boris Sepesi, Roy S Herbst
Journal for ImmunoTherapy of Cancer 2022;10:e003956 (31 May 2022)
POSITION ARTICLE AND GUIDELINE

SOCIETY FOR IMMUNOTHERAPY OF CANCER (SITC) CLINICAL PRACTICE GUIDELINE ON IMMUNOTHERAPY FOR THE TREATMENT OF NONMELANOMA SKIN CANCER

Ann W Silk, Christopher A Barker, Shailender Bhatia, Kathryn B Bollin, Sunandana Chandra, Zeynep Eroglu, Brian R Gastman, Kari L Kendra, Harriet Kluger, Evan J Lipson, Kathleen Madden, David M Miller, Paul Nghiem, Anna C Pavlick, Igor Puzanov, Guilherme Rabinowits, Emily S Ruiz, Vernon K Sondak, Edward A Tavss, Michael T Tetzlaff, Isaac Brownell
Journal for ImmunoTherapy of Cancer 2022;10:e004434 (29 July 2022)
POSITION ARTICLE AND GUIDELINE

NEOADJUVANT IMMUNOTHERAPY OF LOCOREGIONALLY ADVANCED SOLID TUMORS

Ahmad A Tarhini, Jennifer R Eads, Kathleen N Moore, Valerie Tatard-Leitman, John Wright, Patrick M Forde, Robert L Ferris
Journal for ImmunoTherapy of Cancer 2022;10:e005036 (16 August 2022)
POSITION ARTICLE AND GUIDELINE