title: Absence of CD4(+) T cell help generates corrupt CD8(+) effector T cells in sarcoma-bearing Swiss mice treated with NLGP vaccine.
abstract: One of the prime objectives of cancer immunology and immunotherapy is to study the issues related to rescue and/or maintenance of the optimum effector CD8(+) T cell functions by minimizing tumor-induced negative factors. In this regard the influence of host intrinsic CD4(+) helper T cells towards generation and maintenance of CD8(+) effector T cells appears controversial in different experimental settings. Therefore, the present study was aimed to re-analyze the influence of CD4(+) helper T cells towards effector T cells during neem leaf glycoprotein (NLGP)-vaccine-mediated tumor growth restriction. CD4 depletion (mAb; Clone GK1.5) surprisingly resulted in significant increase in CD8(+) T cells in different immune organs from NLGP-treated sarcoma-bearing mice. However, such CD8 surge could not restrict the sarcoma growth in NLGP-treated CD4-depleted mice. Furthermore, CD4 depletion in early phase hinders CD8(+) T cell activation and terminal differentiation by targeting crucial transcription factor Runx3. CD4 depletion decreases accumulation of CD8α(+) dendritic cells within tumor draining lymph node, hampers antigen cross priming and CD86-CD28 interactions for optimum CD8(+) T cell functions. In order to search the mechanism of CD4(+) T cell help on NLGP-mediated CD8 effector functions, the role of CD4(+) helper T cell-derived IL-2 on optimization of CD8 functions was found using STAT5 signaling, but complete response requires physical contact of CD4(+) helper T cells with its CD8 counterpart. In conclusion, it was found that CD4(+) T cell help is not required to generate CD8(+) T cells but was found to be an integral phenomenon in maintenance of its anti-tumor functions even in NLGP-vaccine-mediated sarcoma growth restriction.
authors.affiliation: Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute (CNCI), 37, S.P. Mukherjee Road, Kolkata 700 026, India.
authors.forename: Sarbari
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute (CNCI), 37, S.P. Mukherjee Road, Kolkata 700 026, India.
authors.forename: Madhurima
authors.initials: M
authors.lastname: Sarkar
authors.affiliation: Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute (CNCI), 37, S.P. Mukherjee Road, Kolkata 700 026, India.
authors.forename: Tithi
authors.initials: T
authors.lastname: Ghosh
authors.affiliation: Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute (CNCI), 37, S.P. Mukherjee Road, Kolkata 700 026, India.
authors.forename: Ipsita
authors.initials: I
authors.lastname: Guha
authors.affiliation: Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute (CNCI), 37, S.P. Mukherjee Road, Kolkata 700 026, India.
authors.forename: Avishek
authors.initials: A
authors.lastname: Bhuniya
authors.affiliation: Department of Surgical Oncology and Medical Oncology, Chittaranjan National Cancer Institute (CNCI), 37, S.P. Mukherjee Road, Kolkata 700 026, India.
authors.forename: Jaydip
authors.initials: J
authors.lastname: Biswas
authors.affiliation: Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute (CNCI), 37, S.P. Mukherjee Road, Kolkata 700 026, India.
authors.forename: Atanu
authors.initials: A
authors.lastname: Mallick
authors.affiliation: Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute (CNCI), 37, S.P. Mukherjee Road, Kolkata 700 026, India.
authors.forename: Anamika
authors.initials: A
authors.lastname: Bose
authors.affiliation: Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute (CNCI), 37, S.P. Mukherjee Road, Kolkata 700 026, India. Electronic address: baralrathin@hotmail.com.
authors.forename: Rathindranath
authors.initials: R
authors.lastname: Baral
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000276:immunology*; D031601:Azadirachta / Q000276:immunology; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D019496:Cancer Vaccines / Q000276:immunology*; D048708:Cell Growth Processes; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006131:Growth Inhibitors / Q000276:immunology*; D007376:Interleukin-2 / Q000378:metabolism; D008212:Lymphocyte Depletion; D051379:Mice; D009374:Neoplasms, Experimental; D012509:Sarcoma / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D000970:Antineoplastic Agents; D015704:CD4 Antigens; D016827:CD8 Antigens; D019496:Cancer Vaccines; D006131:Growth Inhibitors; D007376:Interleukin-2
keywords: CD4(+)/CD8(+) T cells; IL-2; Neem leaf glycoprotein; RunX3; Sarcoma