Purpose The presence of tumor-infiltrating lymphocytes (TILs) in tumors is superior to conventional pathologic staging in predicting patient outcome. However, their presence does not define TIL functionality. Here we developed an assay that tests TIL cytotoxicity in patients with locally advanced rectal cancer before definitive treatment, identifying those who will obtain a pathologic complete response (pCR). We also used the assay to demonstrate the rescue of TIL function after checkpoint inhibition blockade (CIB). Patients and Methods Thirty-four consecutive patients were identified initially, with successful completion of the assay before surgery in those 17 patients who underwent full treatment. An in vitro cytotoxic assay of rectal cancer tumoroids cocultured with patient-matched TILs was established and validated. Newly diagnosed patients were recruited with pretreatment biopsy specimens processed within 1 month. Evaluation of TIL-mediated tumoroid lysis was performed by measuring the mean fluorescence intensity of cell death marker, propidium iodide. CIB (anti–programmed cell death protein 1 [anti–PD-1] antibody) response was also assessed in a subset of patient specimens. Results Six of the 17 patients achieved an objective pCR on final evaluation of the resected specimen after neoadjuvant chemoradiotherapy. Cytotoxic killing identified the pCR group with a higher mean fluorescence intensity (27,982 [95% CI, 25,340 to 30,625]) compared with the non-pCR cohort (12,428 [95% CI, 9,434 to 15,423]; p < .001). Assessment of the effectiveness of CIB revealed partial restoration of cytotoxicity in TILs with increased PD-1 expression with anti–PD-1 antibody exposure. Conclusion Evaluating TIL function can be undertaken within weeks of the diagnostic biopsy, affording the potential to alter patient management decisions and refine selection for a watch-and-wait protocol. This cytotoxic assay also has the potential to serve as a platform to assist in the additional development of CIB.

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Introduction: High-risk pulmonary embolism (PE) needs reperfusion therapies. However, it is difficult to make medical decisions when thrombolysis is contraindicated, though pulmonary embolectomy and percutaneous catheter-directed treatment (CTD) are recommended for these patients. Patient concerns: We reported here a case of high-risk PE patient with cardiac arrest (CA), vertebral compression fracture, as well as scalp and frontal hematoma. Diagnosis: The diagnosis of PE was based on computed tomography pulmonary angiography (CTPA) which demonstrated filling defects in the right and left pulmonary arteries. Interventions: Cardiopulmonary resuscitation was performed until the patient returned to idioventricular rhythm 3 minutes after admitted. She suffered another half-hour of hemodynamic disturbance after her shock improved 3 days later. The diagnosis of PE was confirmed by CTPA at that time. The patient did not receive any reperfusion therapies because hemoglobin decreased significantly. Moreover, anticoagulation was postponed for 2 weeks when bleeding appeared to be stopped. She received overlapping treatment with low molecular weight heparin and warfarin for 5 days then warfarin alone and discharged. Outcomes: She was discharged with normal vital signs and neurologically intact. She received anticoagulant therapy with warfarin and international normalized ratio regularly monitored after she was discharged, moreover, the pulmonary artery pressure turned normal, as determined by transthoracic echocardiography 1 month later. The warfarin treatment was discontinued after 12 months and no evidence of recurrence was seen until recently. Conclusions: This is the first case report of PE combined with CA that did not receive reperfusion therapy. We hypothesized that there was a spontaneous resolution in pulmonary emboli.