Comprehensive immune cell profiling depicts an early immune response associated with severe coronavirus disease 2019 in cancer patients

Prashant R Tembhare; Harshini Sriram; Gaurav Chatterjee; Twinkle Khanka; Anant Gokarn; Sumeet Mirgh; Akhil Rajendra; Anumeha Chaturvedi; Sitaram G Ghogale; Nilesh Deshpande; Karishma Girase; Kajal Dalvi; Sweta Rajpal; Nikhil Patkar; Bhakti Trivedi; Amit Joshi; Vedang Murthy; Nitin Shetty; Sudhir Nair; Ashwini More; Sujeet Kamtalwar; Preeti Chavan; Vivek Bhat; Prashant Bhat; Papagudi G Subramanian; Sudeep Gupta; Navin Khattry

doi:10.1111/imcb.12504

Comprehensive immune cell profiling depicts an early immune response associated with severe coronavirus disease 2019 in cancer patients

Immunol Cell Biol. 2022 Jan;100(1):61-73. doi: 10.1111/imcb.12504. Epub 2021 Oct 27.

Authors

Prashant R Tembhare¹, Harshini Sriram¹, Gaurav Chatterjee¹, Twinkle Khanka¹, Anant Gokarn², Sumeet Mirgh², Akhil Rajendra², Anumeha Chaturvedi¹, Sitaram G Ghogale¹, Nilesh Deshpande¹, Karishma Girase¹, Kajal Dalvi¹, Sweta Rajpal¹, Nikhil Patkar¹, Bhakti Trivedi³, Amit Joshi², Vedang Murthy⁴, Nitin Shetty⁵, Sudhir Nair⁶, Ashwini More⁷, Sujeet Kamtalwar⁷, Preeti Chavan⁸, Vivek Bhat⁸, Prashant Bhat⁹, Papagudi G Subramanian¹, Sudeep Gupta², Navin Khattry²

Affiliations

¹ Hematopathology Laboratory, ACTREC, Tata Memorial Center, Homi Bhabha National Institute (HBNI) University, Mumbai, India.
² Department of Medical Oncology, ACTREC, Tata Memorial Center, HBNI University, Mumbai, India.
³ Department of Anesthesiology, Critical Care and Pain, Tata Memorial Center, HBNI University, Mumbai, India.
⁴ Department of Radiation Oncology, ACTREC, Tata Memorial Center, HBNI University, Mumbai, India.
⁵ Department of Radio-Diagnosis, ACTREC, Tata Memorial Center, HBNI University, Mumbai, India.
⁶ Department of Head and Neck Surgical Oncology, ACTREC, Tata Memorial Center, HBNI University, Mumbai, India.
⁷ Department of Medicine, ACTREC, Tata Memorial Center, HBNI University, Mumbai, India.
⁸ Composite Laboratory and Microbiology, ACTREC, Tata Memorial Center, HBNI University, Mumbai, India.
⁹ Medical Administration, ACTREC, Tata Memorial Center, HBNI University, Mumbai, India.

Abstract

Recent studies have highlighted multiple immune perturbations related to severe acute respiratory syndrome coronavirus 2 infection-associated respiratory disease [coronavirus disease 2019 (COVID-19)]. Some of them were associated with immunopathogenesis of severe COVID-19. However, reports on immunological indicators of severe COVID-19 in the early phase of infection in patients with comorbidities such as cancer are scarce. We prospectively studied about 200 immune response parameters, including a comprehensive immune-cell profile, inflammatory cytokines and other parameters, in 95 patients with COVID-19 (37 cancer patients without active disease and intensive chemo/immunotherapy, 58 patients without cancer) and 21 healthy donors. Of 95 patients, 41 had severe disease, and the remaining 54 were categorized as having a nonsevere disease. We evaluated the association of immune response parameters with severe COVID-19. By principal component analysis, three immune signatures defining characteristic immune responses in COVID-19 patients were found. Immune cell perturbations, in particular, decreased levels of circulating dendritic cells (DCs) along with reduced levels of CD4 T-cell subsets such as regulatory T cells (T_regs ), type 1 T helper (Th1) and Th9; additionally, relative expansion of effector natural killer (NK) cells were significantly associated with severe COVID-19. Compared with patients without cancer, the levels of terminal effector CD4 T cells, T_regs , Th9, effector NK cells, B cells, intermediate-type monocytes and myeloid DCs were significantly lower in cancer patients with mild and severe COVID-19. We concluded that severely depleted circulating myeloid DCs and helper T subsets in the initial phase of infection were strongly associated with severe COVID-19 independent of age, type of comorbidity and other parameters. Thus, our study describes the early immune response associated with severe COVID-19 in cancer patients without intensive chemo/immunotherapy.

Keywords: COVID-19; Cancer patients; SARS-CoV-2; immune cell profile; inflammatory cytokines; myeloid dendritic cells; severe disease.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

COVID-19*
Humans
Immunity
Neoplasms* / therapy
SARS-CoV-2
T-Lymphocyte Subsets

Grants and funding

Intramural/Advanced Centre for Treatment, Research and Education in Cancer (ACTREC)