Sachet A. Shukla
A5080842226- Cancer Immunotherapy and Biomarkers
- Cancer Genomics and Diagnostics
- Renal cell carcinoma treatment
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Ferroptosis and cancer prognosis
- Renal and related cancers
- Single-cell and spatial transcriptomics
- Monoclonal and Polyclonal Antibodies Research
- Sarcoma Diagnosis and Treatment
- Chronic Lymphocytic Leukemia Research
- T-cell and B-cell Immunology
- MicroRNA in disease regulation
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- vaccines and immunoinformatics approaches
- Chromatin Remodeling and Cancer
- Lymphoma Diagnosis and Treatment
- Genetic factors in colorectal cancer
- Circular RNAs in diseases
- Bladder and Urothelial Cancer Treatments
- Neuroblastoma Research and Treatments
- Glioma Diagnosis and Treatment
- Peptidase Inhibition and Analysis
Dana-Farber Cancer Institute
2016-2025
The University of Texas MD Anderson Cancer Center
2022-2025
Harvard University
2014-2023
Broad Institute
2013-2022
Massachusetts General Hospital
2019-2021
Brigham and Women's Hospital
2020
Beth Israel Deaconess Medical Center
2020
Massachusetts Institute of Technology
2014-2019
Iowa State University
2012-2018
Community Cancer Center
2014
How the genomic landscape of a tumor shapes and is shaped by anti-tumor immunity has not been systematically explored. Using large-scale data sets solid tissue biopsies, we quantified cytolytic activity local immune infiltrate identified associated properties across 18 types. The number predicted MHC Class I-associated neoantigens was correlated with lower than expected in colorectal other tumors, suggesting immune-mediated elimination. We recurrently mutated genes that showed positive...
The cellular ancestry of tumor antigens One contributing factor in antitumor immunity is the repertoire neoantigens created by genetic mutations within cells. Like corresponding mutations, these show intratumoral heterogeneity. Some are present all cells (clonal), and others only a fraction (subclonal). In study lung cancer melanoma, McGranahan et al. found that high burden clonal correlated with improved patient survival, an increased presence tumor-infiltrating lymphocytes, durable...
Monoclonal antibodies directed against cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), such as ipilimumab, yield considerable clinical benefit for patients with metastatic melanoma by inhibiting immune checkpoint activity, but predictors of response to these therapies remain incompletely characterized. To investigate the roles tumor-specific neoantigens and alterations in tumor microenvironment we analyzed whole exomes from pretreatment biopsies matching germline tissue samples 110...
Abstract Treatment with immune checkpoint blockade (CPB) therapies often leads to prolonged responses in patients metastatic melanoma, but the common mechanisms of primary and acquired resistance these agents remain incompletely characterized have yet be validated large cohorts. By analyzing longitudinal tumor biopsies from 17 melanoma treated CPB therapies, we observed point mutations, deletions or loss heterozygosity (LOH) beta-2-microglobulin ( B2M ), an essential component MHC class I...
Large-scale genomic characterization of tumors from prospective cohort studies may yield new insights into cancer pathogenesis. We performed whole-exome sequencing 619 incident colorectal cancers (CRCs) and integrated the results with tumor immunity, pathology, survival data. identified recurrently mutated genes in CRC, such as BCL9L, RBM10, CTCF, KLF5, that were not previously appreciated this disease. Furthermore, we investigated correlates immune-cell infiltration found higher neoantigen...
Immune checkpoint inhibitor therapy has shown benefit in various cancers, but their potential endometrial cancer (EC) is unknown.Prediction of neoantigen load was performed using sequencing data from the Cancer Genome Atlas set. Evaluation tumor-infiltrating lymphocytes (TILs) and PD-1 PD-L1 expression 63 patients with EC referred to our institution. The predicted median (range) (predicted neoepitopes per sample) proportional mutational load: highest ultramutated polymerase e (POLE) tumors...
Immune checkpoint inhibitors (e.g., anti-PD-1 and anti-PD-L1 antibodies) have demonstrated remarkable efficacy against hypermutated cancers such as melanomas lung carcinomas. One explanation for this effect is that lesions harbor more tumor-specific neoantigens stimulate recruitment of an increased number tumor-infiltrating lymphocytes (TILs), which counterbalanced by overexpression immune checkpoints PD-1 or PD-L1. Given BRCA1/2-mutated high grade serous ovarian (HGSOCs) exhibit a higher...
Pediatric Ewing sarcoma is characterized by the expression of chimeric fusions EWS and ETS family transcription factors, representing a paradigm for studying cancers driven factor rearrangements. In this study, we describe somatic landscape pediatric sarcoma. These tumors are among most genetically normal to date, with only EWS-ETS rearrangements identified in majority tumors. STAG2 loss, however, present more than 15% tumors; occurs point mutation, rearrangement, likely nongenetic...
Abstract To understand the genetic drivers of immune recognition and evasion in colorectal cancer, we analyzed 1,211 cancer primary tumor samples, including 179 classified as microsatellite instability–high (MSI-high). This set includes The Cancer Genome Atlas cohort 592 completed here. MSI-high, a hypermutated, immunogenic subtype had high rate significantly mutated genes important immune-modulating pathways antigen presentation machinery, biallelic losses B2M HLA due to copy-number...