Sanjeeth Rajaram

All Publications

• Genomic predictors of radiation response: recent progress towards personalized radiotherapy for brain metastases. Cell death discovery Harary, P. M., Rajaram, S., Chen, M. S., Hori, Y. S., Park, D. J., Chang, S. D. 2024; 10 (1): 501

  Abstract

  Radiotherapy remains a key treatment modality for both primary and metastatic brain tumors. Significant technological advances in precision radiotherapy, such as stereotactic radiosurgery and intensity-modulated radiotherapy, have contributed to improved clinical outcomes. Notably, however, molecular genetics is not yet widely used to inform brain radiotherapy treatment. By comparison, genetic testing now plays a significant role in guiding targeted therapies and immunotherapies, particularly for brain metastases (BM) of lung cancer, breast cancer, and melanoma. Given increasing evidence of the importance of tumor genetics to radiation response, this may represent a currently under-utilized means of enhancing treatment outcomes. In addition, recent studies have shown potentially actionable mutations in BM which are not present in the primary tumor. Overall, this suggests that further investigation into the pathways mediating radiation response variability is warranted. Here, we provide an overview of key mechanisms implicated in BM radiation resistance, including intrinsic and acquired resistance and intratumoral heterogeneity. We then discuss advances in tumor sampling methods, such as a collection of cell-free DNA and RNA, as well as progress in genomic analysis. We further consider how these tools may be applied to provide personalized radiotherapy for BM, including patient stratification, detection of radiotoxicity, and use of radiosensitization agents. In addition, we describe recent developments in preclinical models of BM and consider their relevance to investigating radiation response. Given the increase in clinical trials evaluating the combination of radiotherapy and targeted therapies, as well as the rising incidence of BM, it is essential to develop genomically informed approaches to enhance radiation response.

  View details for DOI 10.1038/s41420-024-02270-2

  View details for PubMedID 39695143

  View details for PubMedCentralID PMC11655559

• Natural killer cell immunosuppressive function requires CXCR3-dependent redistribution within lymphoid tissues. The Journal of clinical investigation Ali, A., Canaday, L. M., Feldman, H. A., Cevik, H., Moran, M. T., Rajaram, S., Lakes, N., Tuazon, J. A., Seelamneni, H., Krishnamurthy, D., Blass, E., Barouch, D. H., Waggoner, S. N. 2021; 131 (18)

  Abstract

  NK cell suppression of T cells is a key determinant of viral pathogenesis and vaccine efficacy. This process involves perforin-dependent elimination of activated CD4+ T cells during the first 3 days of infection. Although this mechanism requires cell-cell contact, NK cells and T cells typically reside in different compartments of lymphoid tissues at steady state. Here, we showed that NK cell suppression of T cells is associated with transient accumulation of NK cells within T cell-rich sites of the spleen during lymphocytic choriomeningitis virus infection. The chemokine receptor CXCR3 was required for this relocation and suppression of antiviral T cells. Accordingly, NK cell migration was mediated by type I IFN-dependent promotion of CXCR3 ligand expression. In contrast, adenoviral vectors that weakly induced type I IFN and did not stimulate NK cell inhibition of T cells also did not promote measurable redistribution of NK cells to T cell zones. Exogenous IFN rescued NK cell migration during adenoviral vector immunization. Thus, type I IFN and CXCR3 were critical for properly positioning NK cells to constrain antiviral T cell responses. Development of strategies to curtail migration of NK cells between lymphoid compartments may enhance vaccine-elicited immune responses.

  View details for DOI 10.1172/JCI146686

  View details for PubMedID 34314390

  View details for PubMedCentralID PMC8439606

• The Promise and Peril of Natural Killer Cell Therapies in Pulmonary Infection. Immunity Rajaram, S., Canaday, L. M., Ochayon, D. E., Rangel, K. M., Ali, A., Gyurova, I. E., Krishnamurthy, D., Fletcher, J. S., Reighard, S. D., Cox, A., Weirauch, M. T., Kottyan, L. C., Deshmukh, H., Zacharias, W. J., Borchers, M. T., Waggoner, S. N. 2020; 52 (6): 887-889

  View details for DOI 10.1016/j.immuni.2020.04.018

  View details for PubMedID 32405233

  View details for PubMedCentralID PMC7219410

• Moving in for the kill: natural killer cell immunoregulation requires CXCR3 Ali, A., Moran, M. T., Tuazon, J., Rajaram, S., Waggoner, S. N. AMER ASSOC IMMUNOLOGISTS. 2020

  View details for Web of Science ID 000589972401074

• A BAFF-ling new role for NK cells in promoting marginal zone antibacterial resistance during chronic virus infection Ali, A., Cranert, S. A., Moran, M. T., Rajaram, S., Waggoner, S. N. AMER ASSOC IMMUNOLOGISTS. 2020

  View details for Web of Science ID 000589972401066