Natural killer (NK) cells are lymphocytes that are integral to the body’s innate immunity, resulting in a rapid immune response to stressed or infected cells in an antigen-independent manner. The innate immune system plays an important role in the recognition of tumor-derived stress-related factors and is critical to subsequent adaptive immune responses against tumor antigens. The aim of this review is to discuss mechanisms by which tumor cells evade NK cells and to outline strategies that harness NK cells for cancer immunotherapy. We discuss strategies to relieve the exhausted state of NK cells, recent therapies focused on targeting NK-cell-specific activating and inhibitory receptors, the use of cytokines IL-2 and IL-15 to stimulate autologous or allogeneic NK cells, and ongoing trials exploring the use of genetically modified NK cells and chimeric antigen-receptor-modified NK (CAR-NK) cells.

Background: Standard bone marrow biopsy (BMB) and bone involvement with follicular lymphoma (FL) on positron emission tomography (PET)/computed tomography (CT) both predict early clinical failure in FL. The key clinical question is whether PET/CT findings can obviate the need for BMB. The goal of this study was to determine the value of PET/CT in determining bone involvement in FL, using posterior iliac crest BMB as the gold standard.Materials and Methods: A total of 548 patients with newly diagnosed grade 1–3A FL were included. The presence, pattern, and location of bone involvement, spleen involvement, and standardized uptake values (SUVs) in the L3 vertebral body were recorded for all patients and compared with the BMB report.Results: Excluding patients with focal bone lesions on PET/CT, the sensitivity and specificity of PET/CT in detecting bone or marrow involvement, compared with BMB, were 53% and 88%, respectively. The sensitivity and specificity of spleen involvement on PET/CT in predicting a positive BMB were 55% and 86%, respectively. An L3 SUVmax of less than 2.0 resulted in a negative predictive value (NPV) of 96% for marrow involvement on BMB; an L3 SUVmean below 1.4 resulted in an NPV of 100%.Conclusion: In newly diagnosed FL, PET/CT-detected bone and splenic involvement is highly specific for a positive BMB, and very low SUV values (<2.0 SUVmax and < 1.4 SUVmean) in the lumbar spine have a high NPV for a negative BMB. Routine BMB may be obviated in these patients. BMB remains necessary to definitively exclude bone marrow involvement in a large majority of patients with a negative PET.Implications for Practice: Predicting early clinical failure in follicular lymphoma (FL) is important but difficult. Bone marrow involvement by FL is associated with early clinical failure, and determining this involvement is a key component of the initial staging. This study highlights that in certain patients, positron emission tomography/computed tomography is sufficient in determining bone or marrow involvement, without the need for a confirmatory bone marrow biopsy (BMB). An algorithm is provided based on these findings to help clinicians determine which patients would benefit from BMB and when it can be avoided.

Lisocabtagene maraleucel (liso-cel) is one of the three US FDA-approved chimeric antigen receptor T-cell therapies for the treatment of relapsed/refractory (R/R) large B-cell lymphoma (LBCL). TRANS... Plain language summary Chimeric antigen receptor (CAR) T-cell therapy is a type of treatment for large B-cell lymphoma (LBCL). CAR T involves modifying a patient's immune cells (T cells, specifical... Tweetable abstract High-yield review of the use of liso-cel in LBCL. @LurieCancer's @ligordon and @FStPierreMD discuss: ✓ Liso-cel structure, comparison of CAR constructs ✓ Landmark trials for liso...

Background: Internal medicine (IM) residency is a notoriously challenging time generally characterized by long work hours and adjustment to new roles and responsibilities. The COVID-19 pandemic has led to multiple emergent adjustments in training schedules to accommodate increasing needs in patient care. The physician training period, in itself, has been consistently shown to be associated with vulnerability with respect to mental well-being. The impact of the COVID-19 pandemic on the experience of IM trainees is not well established. Objective: Characterize the impact of the COVID-19 pandemic on trainee clinical education, finances, and well-being. Methods: We developed a survey composed of 25 multiple choice questions, 6 of which had an optional short-answer component. The survey was distributed by the American College of Physicians (ACP) to 23,289 IM residents and subspecialty fellows. We received 1,128 complete surveys and an additional 269 partially completed surveys. Results: The majority of respondents reported a disruption in their clinical schedule (76%) and a decrease in both didactic conferences (71%) and protected time for education (56%). A majority of respondents (81%) reported an impact on their well-being with an increase in their level of burnout and 41% of respondents reported a decrease in level of direct supervision. Despite these changes, the majority of trainee respondents (78%) felt well prepared for clinical practice after graduation. Conclusions: These results outline the vulnerable position of internal medicine physicians in training. Preserving educational experiences, adequate supervision, and humane work hours are essential in protecting trainees from mental illness and burnout during global emergencies.

Extranodal (EN) diffuse large B-cell lymphoma (DLBCL) has been historically associated with inferior survival outcomes compared to nodal DLBCL. However, outcomes of patients with EN DLBCL following chimeric antigen receptor T-cell (CAR-T) therapy are not well established. In this multi-center retrospective cohort study, we evaluated the outcomes of patients with EN DLBCL who underwent CAR-T in the relapsed/refractory (R/R) setting. The primary objective was overall survival (OS), while secondary objectives included progression-free survival (PFS), response rates, and toxicity rates. A total of 218 patients were included in the analysis. The most common sites of EN involvement were skin/soft tissue (25%), bone (22%), and lung (17%). Overall response rate (ORR) and complete response rate (CRR) at first post-treatment evaluation were 62% (n = 127) and 40% (n = 82), respectively. Median follow-up was 3.5 years. Median PFS and OS were 4.0 months (95% CI = 3.1–7.2) and 25.7 months (95% CI = 16.1–51.6), respectively. Cytokine release syndrome (CRS) of any grade occurred in 73% (n = 159) of patients, and 6% (n = 12) had grade ≥ 3 CRS. Immune effector cell-associated neurotoxicity syndrome (ICANS) of any grade occurred in 37% (n = 81) of patients, and 19% (n = 41) developed grade ≥ 3 ICANS. In the multivariable analysis, factors that were independently prognostic of inferior OS were 3 or more lines of therapy prior to CAR-T, bulky disease at the time of CAR-T, hepatobiliary, and pancreas involvement, while refractory disease to the most recent therapy prior to CAR-T was associated with inferior PFS. Future studies should further evaluate outcomes of CAR-T in patients with specific EN sites of involvement that appear to be associated with inferior survival such as the liver and pancreas.