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CD8 + tumor-infiltrating lymphocytes (TILs) are increasingly used in oncology as a prognostic and predictive tool to guide patient management. This review summarizes current literature on CD8 + TILs in head and neck squamous cell carcinoma (SCC). Published meta-analyses and clinical trials evaluating CD8 + TILs were analyzed. Consistent positive associations between elevated CD8 + TILs and overall survival have been observed across head and neck sites. CD8 + TILs have been found to predict response to treatment, most commonly immunotherapy, but also chemoradiation. Numerous trials have shown that increased CD8 + TIL frequencies in pretreatment biopsies could identify patients likely to respond to neoadjuvant therapies. CD8 + TIL infiltration has also been elevated in responders both during and after treatment. However, wider adoption of CD8 + TIL quantification as a biomarker has been limited by the need for clinical validation and universal measurement guidelines for head and neck SCC, as there are for other malignancies. Measurement variability includes which tumor compartment is sampled, how TILs are quantified, and which cutoffs are clinically relevant. For several head and neck SCC, measurement of CD8 + TILs in the central or intratumoral compartment, followed by the stromal compartment, has been most consistently associated with survival. Future studies are needed to evaluate subpopulations of CD8 + TILs and biomarker-based treatment selection.

Purpose: Ataxia telangiectasia mutated kinase (ATM) inhibitors are potent radiosensitizers that regulate DNA damage responses and redox metabolism, but they have not been translated clinically because of the potential for excess normal tissue toxicity. Pharmacologic ascorbate (P-AscH - ; intravenous administration achieving mM plasma concentrations) selectively enhances H 2 O 2 -induced oxidative stress and radiosensitization in tumors while acting as an antioxidant and mitigating radiation damage in normal tissues including the bowel. We hypothesized that P-AscH - could enhance the therapeutic index of ATM inhibitor-based chemoradiation by simultaneously enhancing the intended effects of ATM inhibitors in tumors and mitigating off-target effects in adjacent normal tissues., Methods and Materials: Clonogenic survival was assessed in human (human colon tumor [HCT]116, SW480, HT29) and murine (CT26, MC38) colorectal tumor lines and normal cells (human umbilical vein endothelial cell, FHs74) after radiation ± DNA repair inhibitors ± P-AscH - . Tumor growth delay was assessed in mice with HCT116 or MC38 tumors after fractionated radiation (5 Gy × 3) ± the ATM inhibitor KU60019 ± P-AscH - . Intestinal injury, oxidative damage, and transforming growth factor β immunoreactivity were quantified using immunohistochemistry after whole abdominal radiation (10 Gy) ± KU60019 ± P-AscH - . Cell cycle distribution and ATM subcellular localization were assessed using flow cytometry and immunohistochemistry. The role of intracellular H 2 O 2 fluxes was assessed using a stably expressed doxycycline-inducible catalase transgene., Results: KU60019 with P-AscH - enhanced radiosensitization in colorectal cancer models in vitro and in vivo by H 2 O 2 -dependent oxidative damage to proteins and enhanced DNA damage, abrogation of the postradiation G2 cell cycle checkpoint, and inhibition of ATM nuclear localization. In contrast, concurrent P-AscH - markedly reduced intestinal toxicity and oxidative damage with KU60019., Conclusions: We provide evidence that redox modulating drugs, such as P-AscH - , may facilitate the clinical translation of ATM inhibitors by enhancing tumor radiosensitization while simultaneously protecting normal tissues., (Copyright © 2022 Elsevier Inc. All rights reserved.)

TP53 mutation status guides early therapeutic decisions in the treatment of clonal myeloid disorders and serves as a simple means of monitoring response to treatment. We aim here to develop a standardized protocol for evaluating TP 53 mutation status in myeloid disorders using immunohistochemistry assisted by digital image analysis and further compare this approach to manual interpretation alone. To accomplish this, we obtained 118 bone marrow biopsies from patients with hematologic malignancy and molecular testing for mutations associated with acute myeloid leukemia was performed. Clot or core biopsy slides were stained for p53 and digitally scanned. Overall mutation burden was assessed digitally using two different metrics to determine positivity, compared to the results of manual review, and correlated with molecular results. Using this approach, we found that digital analysis of immunohistochemistry stained slides performed worse than manual categorization alone in predicting TP53 mutation status in our cohort (PPV 91%, NPV 100% vs. PPV 100%, NPV 98%). While digital analysis reduced inter- and intraobserver variability when assessing mutation burden, there was poor correlation between the quantity and intensity of p53 staining and molecular analysis (R 2  = 0.204). Therefore, digital image analysis of p53 immunohistochemistry accurately predicts TP53 mutation status as confirmed by molecular testing but does not offer a significant advantage over manual categorization alone. However, this approach offers a highly standardized methodology for monitoring disease status or response to treatment once a diagnosis has been made., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Background: Eosinophilic gastrointestinal disorders, also known as eosinophilic gastroenteritis, are rare inflammatory conditions characterized by eosinophilic infiltration of different parts of the gastrointestinal tract, along with peripheral eosinophilia in most cases. Other known causes for gut eosinophilic infiltration must be excluded to confirm the diagnosis of eosinophilic gastroenteritis. Symptoms of the disorder depend on the affected gastrointestinal tract segment and depth of involvement. Treatment includes systemic glucocorticoids and/or dietary therapy with an empiric elimination diet. Second line therapies include the leukotriene receptor antagonist montelukast, and other anti-allergy drugs such as mast cell stabilizers (including cromolyn and the H1-antihistamine ketotifen), suplatast tosilate which is a selective Th-2 cytokines (IL-4 and IL-5) inhibitor, and the monoclonal anti-IgE antibody omalizumab. We report a case of eosinophilic gastroenteritis who was successfully treated and achieved remission with montelukast as an initial monotherapy. Upon extensive literature review, this represents the second reported adult case of eosinophilic gastroenteritis who responds to montelukast alone as a first line therapy., Case Presentation: A 49-year-old female presented with recurrent abdominal pain, vomiting, diarrhea and unexplained eosinophilia. She was diagnosed with eosinophilic gastroenteritis and was successfully treated with montelukast monotherapy. After 7 days of therapy, the patient responded well and had complete resolution of her gastrointestinal symptoms and peripheral eosinophilia. Patient remained in remission on follow-up after 12 months. We reviewed the literature for leukotriene antagonist use in the treatment of eosinophilic gastroenteritis and included the cases treated with the leukotriene antagonist montelukast as an initial therapy or as a second line therapy for refractory disease., Conclusion: Montelukast may be an effective treatment for eosinophilic gastroenteritis, either alone or in combination with systemic steroids or ketotifen. Our patient is the second reported adult case of eosinophilic gastroenteritis who responded to montelukast alone as a first line therapy. Further studies and clinical trials are required to confirm efficacy compared to standard therapy.