Biology subjects

Panjwani, M. K.

Publications and source records attributed to Panjwani, M. K..

3 recordsLinked to original sources

bioRxiv2026

Polygenic polymorphisms cooperate to drive expansion of HCMV adaptive NK cell and NK-like T cell populations

Human cytomegalovirus (HCMV) infection drives the expansion of several innate and innate-like lymphocyte populations. Characterized by high cell surface expression of NKG2C, these populations include the adaptive CD56+ Fc{epsilon}RI{gamma}- NK cell, an NK-like TCR{beta}+CD8+ T cell population and a V{gamma}9/V{delta}1+ T cells. Beyond NKG2C expression, both the adaptive NK cell and the NK-like T cell population exhibit enhanced cytokine response to antibody-dependent cellular cytotoxicity (ADCC). Expansion of each population is only observed in 30-40% of HCMV+ individuals and is independent of expansion of each other. In this study, we evaluated 200 healthy donors and identified several immunogenetic factors that influence NKG2C expression across the three lymphocyte populations. NKG2C (KLRC2) copy number and allelic polymorphism was associated with NKG2C+ NK cell frequency and surface expression density in HCMV- but not in HCMV+ individuals. Investigating other genetic loci encoding proteins related to adaptive NK function, we found that CD16a and HLA-E alleles act cumulatively with NKG2C copy number to drive NKG2C expression on lymphocytes among HCMV+ individuals. Polymorphism of the NKG2C ligand HLA-E influences strength of NK cell activation via NKG2C, where NK responsiveness was lower in individuals with the HLA-E*01:03 genotype, while CD16a polymorphism influenced strength of ADCC response among NKG2C+ TCR{beta}+CD8+ T cells. Based on these observations, we conclude that genetic polymorphisms in NKG2C, CD16a and HLA-E shape the NKG2C+ repertoire, influence NKG2C-mediated NK function and dictate capacity of ADCC in response to HCMV infection. Immunogenetic polymorphism among NKG2C-related genes therefore tunes innate immunity to HCMV infection providing additional protection beyond adaptive immunity.

immunology↗

bioRxiv2024

Engineered NKG2C+ NK-like T cells exhibit superior antitumor efficacy while mitigating cytokine release syndrome

Engineered T and NK cell therapies have widely been used to treat hematologic malignancies and solid tumors, with promising clinical results. Current chimeric antigen receptor (CAR) T cell therapeutics have, however, been associated with treatment-related adverse events such as cytokine release syndrome (CRS) and are prone to immunologic exhaustion. CAR-NK therapeutics, while not associated with CRS, have limited in vivo persistence. We now demonstrate that an NK-like TCR{beta}+ CD8 T cell subset, identified and expanded ex vivo through its expression of the activating receptor NKG2C (NKG2C+ NK-like T cells), can be transduced to express a second-generation CD19 CAR (1928z), resulting in superior tumor clearance, longer persistence and decreased exhaustion compared to conventional 1928z CAR+ CD8 T cells and 1928z CAR+ NK cells. Moreover, CAR-modified NKG2C+ NK-like T cells resulted in significantly reduced CRS compared to conventional CAR+ CD8 T cells. Similarly, NKG2C+ NK-like T cells engineered with a TCR targeting the NY-ESO-1 antigen exhibit robust tumor control and minimal exhaustion compared to TCR-engineered conventional CD8 T cells. These data establish NKG2C+ NK-like T cells as a robust platform for cell engineering, and offer a safer, more durable alternative to conventional CAR-T and CAR-NK therapies.

immunology↗

bioRxiv2023

Single-Cell Profiling Reveals a Naive-Memory Relationship between CD56bright and Adaptive Human Natural Killer Cells

Development of antigen-specific memory upon pathogen exposure is a hallmark of the adaptive immune system. While natural killer (NK) cells are considered part of the innate immune system, humans exposed to the chronic viral pathogen cytomegalovirus (CMV) often possess a distinct NK cell population lacking in individuals who have not been exposed, termed "adaptive" NK cells. To identify the "naive" population from which this "memory" population derives, we performed phenotypic, transcriptional, and functional profiling of NK cell subsets. We identified immature precursors to the Adaptive NK cells that are equally present in both CMV+ and CMV-individuals, resolved an Adaptive transcriptional state distinct from most mature NK cells and sharing a common gene program with the immature CD56bright population, and demonstrated retention of proliferative capacity and acquisition of superior IFN{gamma} production in the Adaptive population. Furthermore, we distinguish the CD56bright and Adaptive NK populations by expression of the transcription factor CXXC5, positioning these memory NK cells at the inflection point between innate and adaptive lymphocytes.

immunology↗