Myeloid-Derived Suppressor Cells: Therapeutic Target for Gastrointestinal Cancers.

Gastrointestinal cancers represent one of the more challenging cancers to treat. Current strategies to cure and control gastrointestinal (GI) cancers like surgery, radiation, chemotherapy, and immunotherapy have met with limited success, and research has turned towards further characterizing the tumor microenvironment to develop novel therapeutics. Myeloid-derived suppressor cells (MDSCs) have emerged as crucial drivers of pathogenesis and progression within the tumor microenvironment in GI malignancies. Many MDSCs clinical targets have been defined in preclinical models, that potentially play an integral role in blocking recruitment and expansion, promoting MDSC differentiation into mature myeloid cells, depleting existing MDSCs, altering MDSC metabolic pathways, and directly inhibiting MDSC function. This review article analyzes the role of MDSCs in GI cancers as viable therapeutic targets for gastrointestinal malignancies and reviews the existing clinical trial landscape of recently completed and ongoing clinical studies testing novel therapeutics in GI cancers.

Refractory Pure Red Blood Cell Aplasia Secondary to Major ABO-Incompatible Allogeneic Stem Cell Transplantation Successfully Treated With Daratumumab.

Pure red cell aplasia (PRCA) is a rare hematologic phenomenon that is usually associated with inherited genetic mutations such as in Diamond-Blackfan anemia. However, due to the emergence of allogenic stem cell transplantation in the treatment of various malignant and non-malignant disorders, the incidence of PRCA has increased. PRCA following hematopoietic stem cell transplant (HSCT) is more commonly seen in the setting of a major ABO-incompatible transplant. Treatment of allo-HSCT induced PRCA can be initially supportive as it takes time for the bone marrow to fully recover. However, prolonged and/or failure of the bone marrow to recover, significantly increases patient's risk of iron overload in the setting of frequent transfusions. Iron deposition can potentially lead to severe life-threatening multiorgan involvement which can be fatal. Therefore, earlier recognition and intervention with immunomodulators in patients who undergo frequent transfusions can be beneficial to mitigate this risk. Here, we present a case with severe transfusion-dependent PRCA following major ABO-incompatible allo-HSCT successfully treated with daratumumab.

Tumor Immune Profiling-Based Neoadjuvant Immunotherapy for Locally Advanced Melanoma.

BACKGROUND: The frequency of "exhausted" or checkpoint-positive (PD-1+CTLA-4+) cytotoxic lymphocytes (Tex) in the tumor microenvironment is associated with response to anti-PD-1 therapy in metastatic melanoma. The current study determined whether pretreatment Tex cells in locally advanced melanoma predicted response to neoadjuvant anti-PD-1 blockade. METHODS: Pretreatment tumor samples from 17 patients with locally advanced melanoma underwent flow cytometric analysis of pretreatment Tex and regulatory T cell frequency. Patients who met the criteria for neoadjuvant checkpoint blockade were treated with either PD-1 monotherapy or PD-1/CTLA-4 combination therapy. Best overall response was evaluated by response evaluation criteria in solid tumors version 1.1, with recurrence-free survival (RFS) calculated by the Kaplan-Meier test. The incidence and severity of adverse events were tabulated by clinicians using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4. RESULTS: Of the neoadjuvant treated patients, 10 received anti-PD-1 monotherapy and 7 received anti-CTLA-4/PD-1 combination therapy. Of these 17 patients, 12 achieved a complete response, 4 achieved partial responses, and 1 exhibited stable disease. Surgery was subsequently performed for 11 of the 17 patients, and 8 attained a complete pathologic response. Median RFS and overall survival (OS) were not reached. Immune-related adverse events comprised four grade 3 or 4 events, including pneumonitis, transaminitis, and anaphylaxis. CONCLUSION: The results showed high rates of objective response, RFS, and OS for patients undergoing immune profile-directed neoadjuvant immunotherapy for locally advanced melanoma. Furthermore, the study showed that treatment stratification based upon Tex frequency can potentially limit the adverse events associated with combination immunotherapy. These data merit further investigation with a larger validation study.

Low Income and Nonwhite Race are Strongly Associated with Worse Quality of Life in Patients with Nephrolithiasis.

PURPOSE: Kidney stones are a source of significant morbidity which have been shown to negatively impact health related quality of life. We sought to understand the association between health related quality of life, socioeconomic status and race among patients with kidney stones. MATERIALS AND METHODS: Patients with stones at a total of 11 stone centers across the United States completed the WISQOL (Wisconsin Stone Quality of Life questionnaire). The patient ZIP Code™ was used to estimate household income. A mixed effects regression model was constructed for analysis with ZIP Code as the random intercept. RESULTS: A total of 2,057 stone formers completed the WISQOL. Lower income was independently associated with significantly lower health related quality of life (ß = 0.372, p = 0.014), as were nonwhite race (ß = -0.299, p = 0.001), unemployed work status (ß = -0.291, p = 0.008), female gender (ß = -0.204, p <0.001), body mass index greater than 40 kg/m2 (ß = -0.380, p <0.001), 5 or more medical comorbidities (ß = -0.354, p = 0.001), severe recurrent stone formation (ß = -0.146, p = 0.045), enrollment at an acute care visit, or a preoperative or postoperative appointment (ß = -0.548, p <0.001) and recent stone symptoms (ß = -0.892, p <0.001). CONCLUSIONS: Lower income, nonwhite race and unemployed work status were independently associated with lower health related quality of life among patients with kidney stones. While clinical characteristics such as body mass and stone disease severity were also associated with health related quality of life, this study shows that socioeconomic factors are similarly important. Further research to understand the specific mechanisms by which socioeconomic status and race impact health may lend insight into methods to optimize clinical treatment of stone formers and patients with other chronic diseases.